Affinage

INHA

Inhibin alpha chain · UniProt P05111

Round 2 corrected
Length
366 aa
Mass
39.7 kDa
Annotated
2026-04-28
130 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

INHA encodes the alpha subunit of inhibin, a disulfide-linked heterodimeric glycoprotein (inhibin A = α:βA; inhibin B = α:βB) that functions as a gonad-specific tumor suppressor and a competitive antagonist of activin signaling (PMID:3016724, PMID:3754442, PMID:1448148). Inhibin binds the type II activin receptor (ActRII) via its beta subunit at a hydrophobic interface (Phe42, Trp60, Phe83) shared with activin, but fails to recruit the type I receptor ALK4, thereby acting as a dominant-negative blocker of activin-induced Smad signaling; high-affinity antagonism requires the co-receptor betaglycan (PMID:7890768, PMID:10652306, PMID:10746731). Targeted deletion of Inha in mice causes fully penetrant gonadal stromal tumors, and genetic epistasis studies in mouse and zebrafish demonstrate that INHA-containing inhibin restrains activin/GDF9-driven granulosa cell proliferation, folliculogenesis, and estradiol-dependent oocyte growth (PMID:1448148, PMID:23446452, PMID:37713421).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 1986 High

    Cloning and sequencing of the INHA gene and its two beta subunit partners established that inhibin is a heterodimeric glycoprotein (α:βA or α:βB) encoded by a single-copy gene on chromosome 2q, expressed specifically in the gonads under gonadotropin control.

    Evidence cDNA cloning from porcine ovary and human placenta, Northern blots, Southern blot analysis of somatic cell hybrids, in situ hybridization, genomic sequencing

    PMID:2767687 PMID:3016724 PMID:3754442 PMID:3758355

    Open questions at the time
    • Post-translational processing steps of the alpha subunit precursor were not fully characterized
    • Gonadal cell types producing INHA protein were not resolved at single-cell level
  2. 1992 High

    Targeted deletion of the Inha gene demonstrated that the alpha subunit is an essential tumor suppressor, as Inha-null mice universally develop gonadal stromal tumors — the first genetic proof of a secreted hormone acting as a tumor suppressor.

    Evidence Homologous recombination knockout in mouse ES cells, histopathological analysis showing 100% penetrance of gonadal tumors

    PMID:1448148

    Open questions at the time
    • Downstream signaling events linking loss of inhibin to tumorigenesis were not defined
    • Whether tumor suppression is cell-autonomous or paracrine was unresolved
  3. 1995 High

    Biochemical dissection of inhibin's antagonism of activin revealed a dominant-negative mechanism: inhibin binds ActRII through its beta subunit but cannot recruit the type I receptor, blocking activin signaling complex formation.

    Evidence Receptor crosslinking, competitive binding assays, and DNA synthesis measurement in HepG2 cells

    PMID:7890768

    Open questions at the time
    • The contribution of the alpha subunit to receptor binding was unclear
    • Identity of the postulated inhibin-specific co-receptor remained unknown
  4. 2000 High

    Identification of betaglycan as the inhibin co-receptor and mapping of the shared ActRII binding interface (Phe42, Trp60, Phe83) completed the model of inhibin's competitive antagonism, explaining how inhibin achieves high-affinity activin blockade in co-receptor-expressing tissues.

    Evidence Crosslinking, co-immunoprecipitation, transfection-based binding and functional assays (betaglycan); alanine scanning mutagenesis of ActRII extracellular domain with crosslinking and signaling assays

    PMID:10652306 PMID:10746731

    Open questions at the time
    • Structural basis of the ternary inhibin–betaglycan–ActRII complex was not determined at atomic resolution
    • Whether betaglycan mediates inhibin tumor suppression in vivo was untested
  5. 2013 High

    Genetic epistasis in Inha/Gdf9 double-knockout mice revealed that GDF9 drives the initial follicular growth defects in Inha-null ovaries but paradoxically suppresses tumor initiation, separating the folliculogenesis and tumor suppression functions of inhibin.

    Evidence Double knockout mouse genetics (Inha × Gdf9), histological follicle staging, immunohistochemistry, qRT-PCR

    PMID:23446452

    Open questions at the time
    • Cell-type-specific signaling mediating GDF9's tumor-suppressive role in the Inha-null context was undefined
    • Whether activin betaB upregulation is the proximate tumorigenic signal was not directly tested
  6. 2023 High

    Triple-mutant zebrafish genetics demonstrated that loss of inha rescues bmp15-deficient follicle arrest through derepression of activin betaAa, which drives estradiol biosynthesis and vitellogenin-dependent oocyte growth — establishing that inhibin's core reproductive function is to restrain activin-mediated estradiol production.

    Evidence CRISPR/Cas9 single, double, and triple knockouts (bmp15, inha, inhbaa); RNAseq; serum estradiol and vitellogenin measurements; aromatase inhibitor treatment and E2 rescue

    PMID:37713421

    Open questions at the time
    • Whether this estradiol-mediated mechanism operates in mammalian granulosa cells remains untested
    • The direct activin target genes mediating aromatase induction were not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structure of the full inhibin heterodimer in complex with betaglycan and ActRII exists, and the mechanism by which loss of inhibin triggers stromal tumor initiation (as opposed to hyperplasia) has not been resolved at the signaling pathway level.
  • Atomic-resolution structure of the inhibin–betaglycan–ActRII ternary complex is lacking
  • Cell-autonomous versus paracrine mechanisms of tumor suppression in the gonad remain undefined
  • Whether INHA mutations contribute to human gonadal tumorigenesis is not established by direct genetic evidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0048018 receptor ligand activity 3
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 2
Partners
ACVR2AGDF9INHBAINHBBTGFBR3
Complex memberships
Inhibin A (alpha:betaA heterodimer)Inhibin B (alpha:betaB heterodimer)Inhibin–betaglycan–ActRII ternary complex

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 The human INHA gene encodes the alpha subunit of inhibin, a glycoprotein whose cDNA was cloned from porcine ovary and human placenta; the alpha subunit is synthesized as a larger precursor and the mRNA is expressed specifically in the gonads, with expression inducible by gonadotropins. cDNA cloning and nucleotide sequencing, Northern blot expression analysis Proceedings of the National Academy of Sciences of the United States of America High 3016724
1986 Human inhibin exists as two heterodimeric forms (inhibin A and inhibin B), each composed of a common alpha subunit (INHA product) disulfide-linked to one of two distinct beta subunits (beta A or beta B); the human alpha subunit shares 84% sequence conservation with its porcine counterpart. cDNA cloning and nucleotide sequencing of subunit precursors Biochemical and biophysical research communications High 3754442
1986 The human INHA (alpha subunit) gene is present as a single copy and maps to chromosome 2q33-qter, while the beta B subunit gene maps to chromosome 2cen-q13; both alpha and beta B map to mouse chromosome 1. Southern blot analysis of somatic cell hybrid DNAs and in situ hybridization Genomics High 2767687
1986 The INHA gene has a defined genomic structure; cloning and sequencing of the human genomic locus confirmed single-copy status and provided the genomic sequence of the alpha subunit. Southern blot hybridization, cloning from lambda genomic libraries, DNA sequencing FEBS letters High 3758355
1991 Follistatin binds to inhibin (INHA-containing heterodimer) through the common beta subunit, not the alpha subunit; inhibin A has only one follistatin binding site (through its beta subunit), whereas activin A has two, establishing that the INHA alpha subunit does not mediate follistatin binding. Double-ligand blotting technique Endocrinology Medium 2036994
1992 Targeted deletion of the alpha-inhibin gene (Inha) in mice results in development of mixed or incompletely differentiated gonadal stromal tumors in every animal, establishing INHA as a gonad-specific tumor suppressor gene and a critical negative regulator of gonadal stromal cell proliferation. Homologous recombination in mouse embryonic stem cells (gene knockout), histopathological analysis Nature High 1448148
1995 Inhibin (INHA-containing heterodimer) antagonizes activin-mediated inhibition of hepatocyte DNA synthesis through a dominant-negative mechanism: inhibin binds ActRII via its beta subunit and competes with activin for ActRII binding, but fails to recruit the type I receptor (SKR2), thereby blocking formation of the active ActRII-activin-SKR2 signaling complex. Receptor crosslinking assays, competitive binding assays, DNA synthesis measurement in HepG2 cells The Journal of biological chemistry High 7890768
1997 Inhibin's antagonism of activin-induced erythroid differentiation and receptor heteromerization is mediated through competition for the type II activin receptor (ActRII), and requires an additional inhibin-specific binding component beyond ActRII itself. Stable inducible cell lines overexpressing ActRII/ALK4; activin/inhibin treatment assays; hemoglobin accumulation and proliferation assays Molecular and cellular biology High 9032295
2000 Betaglycan (type III TGF-beta receptor) functions as a high-affinity co-receptor for inhibin (INHA-containing heterodimer) together with ActRII; betaglycan enhances inhibin binding to cells co-expressing ActRII, inhibin forms crosslinked complexes with both betaglycan and ActRII, and betaglycan confers inhibin responsiveness to cell lines otherwise insensitive to inhibin, enabling functional antagonism of activin signaling. Crosslinking assays, co-immunoprecipitation, binding studies in transfected cells, functional activin antagonism assays Nature High 10746731
2000 Three hydrophobic residues on ActRII (Phe42, Trp60, Phe83) form a critical binding surface required for functional interactions with both activin and inhibin (INHA-containing heterodimer); alanine substitution at each position disrupts inhibin binding, confirming that inhibin binds ActRII at the same interface as activin. Alanine scanning mutagenesis of ActRII extracellular domain, crosslinking binding assays, signaling assays in corticotroph cell lines The Journal of biological chemistry High 10652306
2000 The activin betaC subunit can dimerize with betaA and betaB subunits in vitro but cannot form a heterodimer with the inhibin alpha subunit (INHA), establishing that the alpha subunit has selective dimerization specificity restricted to beta A and beta B subunits. Mammalian cell co-expression and dimerization assays, immunolocalization The Journal of clinical endocrinology and metabolism Medium 11134153
2009 In zebrafish, the inha (inhibin alpha subunit ortholog) is expressed exclusively in somatic follicle cells of the ovary (not in oocytes, pituitary, or brain); FSH (but not LH) significantly stimulates inha expression in cultured ovarian fragments; and human inhibin A inhibits oocyte maturation in vitro, suggesting a conserved negative feedback loop between pituitary FSH and ovarian inhibin. In situ hybridization, RT-PCR tissue expression profiling, recombinant FSH/LH treatment of cultured ovarian fragments, in vitro oocyte maturation assay Reproduction (Cambridge, England) Medium 19602521
2013 In Inha-null prepubertal mouse ovaries, GDF9 drives initial defects in preantral follicle growth; deletion of Gdf9 from Inha(-/-) mice rescues early follicle growth defects and reduces the activin/inhibin beta B subunit (Inhbb) upregulation seen in Inha(-/-) ovaries, but paradoxically accelerates pretumor lesion onset, establishing a sequential genetic epistasis where GDF9 promotes defective folliculogenesis and suppresses tumor initiation in the Inha-null context. Double knockout mouse genetics (Inha x Gdf9), histological follicle staging, immunohistochemistry, qRT-PCR Biology of reproduction High 23446452
2023 Loss of inha (inhibin alpha) in zebrafish partially rescues the follicle development arrest and sex reversal caused by bmp15 deficiency; the bmp15/inha double mutant progresses to mid-vitellogenic follicle stage with yolk accumulation, and this rescue is dependent on increased inhbaa (activin betaAa) expression driving estradiol production, vitellogenin biosynthesis, and oocyte uptake via LRP receptors — establishing that INHA/inhibin restrains activin-mediated pathways that BMP15 normally promotes to sustain folliculogenesis. CRISPR/Cas9 knockouts (bmp15, inha, inhbaa single, double, and triple mutants), follicle staging, RNAseq transcriptome analysis, serum estradiol and vitellogenin measurements, aromatase inhibitor treatment, E2 rescue experiments PLoS genetics High 37713421

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
1994 inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science (New York, N.Y.) 1115 8284673
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1992 Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 818 1448148
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1998 Modification of the NADH of the isoniazid target (InhA) from Mycobacterium tuberculosis. Science (New York, N.Y.) 543 9417034
2000 Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature 478 10746731
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1986 Structure of two human ovarian inhibins. Biochemical and biophysical research communications 324 3754442
1991 Follistatin binds to both activin and inhibin through the common subunit. Endocrinology 270 2036994
1989 Inhibin as a marker for granulosa-cell tumors. The New England journal of medicine 270 2770810
2003 The isoniazid-NAD adduct is a slow, tight-binding inhibitor of InhA, the Mycobacterium tuberculosis enoyl reductase: adduct affinity and drug resistance. Proceedings of the National Academy of Sciences of the United States of America 262 14623976
1986 Inhibin A-subunit cDNAs from porcine ovary and human placenta. Proceedings of the National Academy of Sciences of the United States of America 260 3016724
2002 Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium. Experimental biology and medicine (Maywood, N.J.) 259 12324653
1988 Erythroid differentiation factor is encoded by the same mRNA as that of the inhibin beta A chain. Proceedings of the National Academy of Sciences of the United States of America 254 3267209
2006 Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid. Nature medicine 234 16906155
2003 ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. Antimicrobial agents and chemotherapy 225 14638486
1999 Crystal structure of the Mycobacterium tuberculosis enoyl-ACP reductase, InhA, in complex with NAD+ and a C16 fatty acyl substrate. The Journal of biological chemistry 219 10336454
2000 Inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis, by triclosan and isoniazid. Biochemistry 200 10869170
2007 Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. American journal of human genetics 183 17847007
2006 High affinity InhA inhibitors with activity against drug-resistant strains of Mycobacterium tuberculosis. ACS chemical biology 183 17163639
2002 Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis. Molecular microbiology 163 12406221
1999 Genetic evidence that InhA of Mycobacterium smegmatis is a target for triclosan. Antimicrobial agents and chemotherapy 158 10049298
1997 Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation. Molecular and cellular biology 144 9032295
1995 Effect of inhA and katG on isoniazid resistance and virulence of Mycobacterium bovis. Molecular microbiology 132 7623658
1995 Characterization of the katG and inhA genes of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy 131 8585728
2000 Inhibin: a candidate gene for premature ovarian failure. Human reproduction (Oxford, England) 130 11098038
2010 A slow, tight binding inhibitor of InhA, the enoyl-acyl carrier protein reductase from Mycobacterium tuberculosis. The Journal of biological chemistry 128 20200152
2004 Granular cell tumor: immunohistochemical assessment of inhibin-alpha, protein gene product 9.5, S100 protein, CD68, and Ki-67 proliferative index with clinical correlation. Archives of pathology & laboratory medicine 127 15214825
2014 Inhibin at 90: from discovery to clinical application, a historical review. Endocrine reviews 126 25051334
1989 Activin B: precursor sequences, genomic structure and in vitro activities. Molecular endocrinology (Baltimore, Md.) 125 2575216
1999 Roles of tyrosine 158 and lysine 165 in the catalytic mechanism of InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis. Biochemistry 113 10521269
1995 Inhibin antagonizes inhibition of liver cell growth by activin by a dominant-negative mechanism. The Journal of biological chemistry 110 7890768
2007 Statistically significant changes of antimüllerian hormone and inhibin levels during the physiologic menstrual cycle in reproductive age women. Fertility and sterility 107 17603052
2010 A large-scale candidate gene association study of age at menarche and age at natural menopause. Human genetics 106 20734064
1986 Human inhibin genes. Genomic characterisation and sequencing. FEBS letters 105 3758355
2015 Direct inhibitors of InhA are active against Mycobacterium tuberculosis. Science translational medicine 102 25568071
2013 High-level resistance to isoniazid and ethionamide in multidrug-resistant Mycobacterium tuberculosis of the Lisboa family is associated with inhA double mutations. The Journal of antimicrobial chemotherapy 99 23539241
2000 Genomic mutations in the katG, inhA and aphC genes are useful for the prediction of isoniazid resistance in Mycobacterium tuberculosis isolates from Kwazulu Natal, South Africa. Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 99 10897383
2007 Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides. Bioorganic & medicinal chemistry 98 17723305
2000 Localization of activin beta(A)-, beta(B)-, and beta(C)-subunits in humanprostate and evidence for formation of new activin heterodimers of beta(C)-subunit. The Journal of clinical endocrinology and metabolism 92 11134153
1996 Biochemical and genetic data suggest that InhA is not the primary target for activated isoniazid in Mycobacterium tuberculosis. The Journal of infectious diseases 92 8896513
1993 Activin A induces apoptotic cell death. Biochemical and biophysical research communications 90 8267637
2003 Mutations in katG, inhA, and ahpC genes of Brazilian isoniazid-resistant isolates of Mycobacterium tuberculosis. Journal of clinical microbiology 89 12958298
2000 Identification of a binding site on the type II activin receptor for activin and inhibin. The Journal of biological chemistry 89 10652306
1989 Mapping of genes for inhibin subunits alpha, beta A, and beta B on human and mouse chromosomes and studies of jsd mice. Genomics 85 2767687
2009 Correlations of mutations in katG, oxyR-ahpC and inhA genes and in vitro susceptibility in Mycobacterium tuberculosis clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America. BMC microbiology 83 19228426
2016 Detection of katG and inhA mutations to guide isoniazid and ethionamide use for drug-resistant tuberculosis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 74 27393546
2010 Phosphorylation of enoyl-acyl carrier protein reductase InhA impacts mycobacterial growth and survival. The Journal of biological chemistry 67 20864541
2003 Isoniazid activation defects in recombinant Mycobacterium tuberculosis catalase-peroxidase (KatG) mutants evident in InhA inhibitor production. Antimicrobial agents and chemotherapy 67 12543676
2002 Mn(III) pyrophosphate as an efficient tool for studying the mode of action of isoniazid on the InhA protein of Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy 66 12069966
1998 The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance. Microbiology (Reading, England) 64 9802011
2016 Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor. EBioMedicine 61 27428438
2014 Design, synthesis, and evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase (InhA) for the treatment of tuberculosis. Journal of medicinal chemistry 59 25517015
2014 A structural and energetic model for the slow-onset inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA. ACS chemical biology 58 24527857
2003 Inhibition of InhA activity, but not KasA activity, induces formation of a KasA-containing complex in mycobacteria. The Journal of biological chemistry 58 12654922
2011 Novel inhibitors of InhA efficiently kill Mycobacterium tuberculosis under aerobic and anaerobic conditions. Antimicrobial agents and chemotherapy 57 21628538
2021 Mycobacterium enoyl acyl carrier protein reductase (InhA): A key target for antitubercular drug discovery. Bioorganic chemistry 54 34392175
2013 Discovery of new inhibitors of Mycobacterium tuberculosis InhA enzyme using virtual screening and a 3D-pharmacophore-based approach. Journal of chemical information and modeling 54 23889525
2010 Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis. Molecular microbiology 53 21143326
2001 Identification of genes involved in the activation of the Bacillus thuringiensis inhA metalloprotease gene at the onset of sporulation. Microbiology (Reading, England) 51 11429458
2017 Evaluating the Contribution of Transition-State Destabilization to Changes in the Residence Time of Triazole-Based InhA Inhibitors. Journal of the American Chemical Society 49 28151657
1997 Usefulness of Mycobacterium tuberculosis genomic mutations in the genes katG and inhA for the prediction of isoniazid resistance. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 49 9432394
2016 Discovery of cofactor-specific, bactericidal Mycobacterium tuberculosis InhA inhibitors using DNA-encoded library technology. Proceedings of the National Academy of Sciences of the United States of America 47 27864515
2018 An overview on crystal structures of InhA protein: Apo-form, in complex with its natural ligands and inhibitors. European journal of medicinal chemistry 46 29407960
2014 Time-dependent diaryl ether inhibitors of InhA: structure-activity relationship studies of enzyme inhibition, antibacterial activity, and in vivo efficacy. ChemMedChem 46 24616444
2011 Synthesis and biological activities of triazole derivatives as inhibitors of InhA and antituberculosis agents. European journal of medicinal chemistry 46 21944473
2018 Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant Mycobacterium tuberculosis in Kyrgyz Republic. BMC microbiology 41 29566660
2015 Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach. Journal of structural biology 39 25891098
2005 Molecular dynamics simulation studies of the wild-type, I21V, and I16T mutants of isoniazid-resistant Mycobacterium tuberculosis enoyl reductase (InhA) in complex with NADH: toward the understanding of NADH-InhA different affinities. Biophysical journal 37 15908576
2012 Cross-docking study on InhA inhibitors: a combination of Autodock Vina and PM6-DH2 simulations to retrieve bio-active conformations. Organic & biomolecular chemistry 36 22751934
2006 Molecular characterization of isoniazid resistance in Mycobacterium tuberculosis: identification of a novel mutation in inhA. Antimicrobial agents and chemotherapy 36 16495272
2018 The impact of combined gene mutations in inhA and ahpC genes on high levels of isoniazid resistance amongst katG non-315 in multidrug-resistant tuberculosis isolates from China. Emerging microbes & infections 35 30446638
2016 N-Benzyl-4-((heteroaryl)methyl)benzamides: A New Class of Direct NADH-Dependent 2-trans Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity. ChemMedChem 35 26934341
2011 Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages. PloS one 35 21437287
2007 Development of modern InhA inhibitors to combat drug resistant strains of Mycobacterium tuberculosis. Current topics in medicinal chemistry 35 17346194
2020 Fragment-Based Design of Mycobacterium tuberculosis InhA Inhibitors. Journal of medicinal chemistry 34 32240584
2019 Discovery of New and Potent InhA Inhibitors as Antituberculosis Agents: Structure-Based Virtual Screening Validated by Biological Assays and X-ray Crystallography. Journal of chemical information and modeling 34 31820972
2009 Characterization of inhibin alpha subunit (inha) in the zebrafish: evidence for a potential feedback loop between the pituitary and ovary. Reproduction (Cambridge, England) 34 19602521
2015 Rational Modulation of the Induced-Fit Conformational Change for Slow-Onset Inhibition in Mycobacterium tuberculosis InhA. Biochemistry 33 26147157
2010 Detection of rpoB, katG and inhA gene mutations in Mycobacterium tuberculosis clinical isolates from Chongqing as determined by microarray. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 33 20491829
2015 Design, synthesis and evaluation of new GEQ derivatives as inhibitors of InhA enzyme and Mycobacterium tuberculosis growth. European journal of medicinal chemistry 32 26142487
2015 High Prevalence of inhA Promoter Mutations among Patients with Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa. PloS one 32 26332235
2018 Discovery of a cofactor-independent inhibitor of Mycobacterium tuberculosis InhA. Life science alliance 31 30456352
2013 The mutations of katG and inhA genes of isoniazid-resistant Mycobacterium tuberculosis isolates in Taiwan. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 31 24184004
2014 Biological evaluation of potent triclosan-derived inhibitors of the enoyl-acyl carrier protein reductase InhA in drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis. ChemMedChem 29 25165007
2020 Discovery of hydrazone containing thiadiazoles as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors. European journal of medicinal chemistry 27 31951850
2015 A virtual screen discovers novel, fragment-sized inhibitors of Mycobacterium tuberculosis InhA. Journal of chemical information and modeling 27 25636146
2013 Design, chemical synthesis of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives and biological activity against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis. European journal of medicinal chemistry 26 24140915
2010 Recent progress in the identification and development of InhA direct inhibitors of Mycobacterium tuberculosis. Mini reviews in medicinal chemistry 26 20408801
2016 Discovery of Mycobacterium tuberculosis InhA Inhibitors by Binding Sites Comparison and Ligands Prediction. Journal of medicinal chemistry 25 27936766
2023 Recent Advances in Anti-Tuberculosis Drug Discovery Based on Hydrazide-Hydrazone and Thiadiazole Derivatives Targeting InhA. Pharmaceuticals (Basel, Switzerland) 24 37111241
2017 Multiple receptor conformers based molecular docking study of fluorine enhanced ethionamide with mycobacterium enoyl ACP reductase (InhA). Journal of molecular graphics & modelling 24 28957755
2009 A large-scale association study to assess the impact of known variants of the human INHA gene on premature ovarian failure. Human reproduction (Oxford, England) 24 19363042
2019 Intrabacterial Metabolism Obscures the Successful Prediction of an InhA Inhibitor of Mycobacterium tuberculosis. ACS infectious diseases 23 31625383
2015 An Effective Approach for Clustering InhA Molecular Dynamics Trajectory Using Substrate-Binding Cavity Features. PloS one 22 26218832
2021 New InhA Inhibitors Based on Expanded Triclosan and Di-Triclosan Analogues to Develop a New Treatment for Tuberculosis. Pharmaceuticals (Basel, Switzerland) 21 33919737
2021 Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme. Journal of enzyme inhibition and medicinal chemistry 21 34210233
2014 Development of 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives as novel enoyl-acyl carrier protein reductase (InhA) inhibitors for the treatment of tuberculosis. European journal of medicinal chemistry 21 25218910
2012 Bacillus anthracis protease InhA regulates BslA-mediated adhesion in human endothelial cells. Cellular microbiology 21 22452315
2019 First triclosan-based macrocyclic inhibitors of InhA enzyme. Bioorganic chemistry 20 31855823
2008 Function of heterologous Mycobacterium tuberculosis InhA, a type 2 fatty acid synthase enzyme involved in extending C20 fatty acids to C60-to-C90 mycolic acids, during de novo lipoic acid synthesis in Saccharomyces cerevisiae. Applied and environmental microbiology 20 18552191
2008 Binding of the tautomeric forms of isoniazid-NAD adducts to the active site of the Mycobacterium tuberculosis enoyl-ACP reductase (InhA): a theoretical approach. Journal of molecular graphics & modelling 19 18955002
2019 In Silico Repositioning of Cannabigerol as a Novel Inhibitor of the Enoyl Acyl Carrier Protein (ACP) Reductase (InhA). Molecules (Basel, Switzerland) 18 31311157
2012 Detection of genomic mutations in katG, inhA and rpoB genes of Mycobacterium tuberculosis isolates using polymerase chain reaction and multiplex allele-specific polymerase chain reaction. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases 18 22358357
2023 Rescue of bmp15 deficiency in zebrafish by mutation of inha reveals mechanisms of BMP15 regulation of folliculogenesis. PLoS genetics 17 37713421
2022 Efficacy and Mode of Action of a Direct Inhibitor of Mycobacterium abscessus InhA. ACS infectious diseases 17 36107992
2020 Mutations in rpoB and katG genes and the inhA operon in multidrug-resistant Mycobacterium tuberculosis isolates from Zambia. Journal of global antimicrobial resistance 17 32169686
2019 Discovery of novel N-methyl carbazole tethered rhodanine derivatives as direct inhibitors of Mycobacterium tuberculosis InhA. Bioorganic & medicinal chemistry letters 17 31227345
2018 Pharmacophore mapping, molecular docking, chemical synthesis of some novel pyrrolyl benzamide derivatives and evaluation of their inhibitory activity against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis. Bioorganic chemistry 17 30223149
2020 Inhibition of Mycobacterium tuberculosis InhA: Design, synthesis and evaluation of new di-triclosan derivatives. Bioorganic & medicinal chemistry 16 33007556
2015 Molecular docking studies on InhA, MabA and PanK enzymes from Mycobacterium tuberculosis of ellagic acid derivatives from Ludwigia adscendens and Trewia nudiflora. In silico pharmacology 16 26820895
2013 GDF9 modulates the reproductive and tumor phenotype of female inha-null mice. Biology of reproduction 16 23446452
2023 Computational insights into potential marine natural products as selective inhibitors of Mycobacterium tuberculosis InhA: A structure-based virtual screening study. Computational biology and chemistry 15 38086160
2021 Design and synthesis of 2-(2-isonicotinoylhydrazineylidene)propanamides as InhA inhibitors with high antitubercular activity. European journal of medicinal chemistry 15 34198149
2020 Structural Basis for Inhibition of Enoyl-[Acyl Carrier Protein] Reductase (InhA) from Mycobacterium tuberculosis. Current medicinal chemistry 15 30501592
2015 Discovery of InhA inhibitors with anti-mycobacterial activity through a matched molecular pair approach. European journal of medicinal chemistry 15 25778993
2015 Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy. BMC medical genetics 15 26654447
2012 Can inhA mutation predict ethionamide resistance? The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 15 23146620
2007 Probing mechanisms of resistance to the tuberculosis drug isoniazid: Conformational changes caused by inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis. Protein science : a publication of the Protein Society 15 17600151
2024 Unlocking InhA: Novel approaches to inhibit Mycobacterium tuberculosis. Bioorganic chemistry 14 38460337
2022 Identification of Novel Inhibitor of Enoyl-Acyl Carrier Protein Reductase (InhA) Enzyme in Mycobacterium tuberculosis from Plant-Derived Metabolites: An In Silico Study. Antibiotics (Basel, Switzerland) 14 36009907
2020 Pattern of InhA and KatG mutations in isoniazid monoresistant Mycobacterium tuberculosis isolates. Lung India : official organ of Indian Chest Society 14 32367844
2018 Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA. ChemMedChem 14 29399991
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