golidocitinib   Click here for help

GtoPdb Ligand ID: 10744

Synonyms: AZD-4205 | AZD4205 | compound 21 [PMID: 32297743] | example 32 [US9714236B2] [1] | JAK1-IN-3
Compound class: Synthetic organic
Comment: AZD4205 is a selective, orally bioavailable, ATP-competitive inhibitor of Janus kinase 1 (JAK1) that was developed by Dizal Pharmaceutical Company [2]. It has been shown to enhance antitumour activity in combination with osimertinib (an approved EGFR inhibitor) in a preclinical non-small cell lung cancer xenograft model. A higher drug concentration within the gastrointestinal tract relative to plasma in preclinical models suggests potential to treat inflammatory bowel disease. Persistently activated STAT3 has been shown to be oncogenic, and drives expression of cellular proteins which contribute to central processes in cancer progression (survival, proliferation, invasion, angiogenesis). JAK1 is the key Janus kinase responsible for cytokine-mediated STAT3 activation.
The chemical structure of AZD4205 matches that for the INN golidocitinib which was surfaced in WHO Proposed list 125 in July 2021.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 116.23
Molecular weight 489.26
XLogP 1.86
No. Lipinski's rules broken 0
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Canonical SMILES COc1nn(cc1Nc1nccc(n1)c1c[nH]c2c1cccc2NC(=O)[C@H](N1CCN(CC1)C)C)C
Isomeric SMILES COc1nn(cc1Nc1nccc(n1)c1c[nH]c2c1cccc2NC(=O)[C@H](N1CCN(CC1)C)C)C
InChI InChI=1S/C25H31N9O2/c1-16(34-12-10-32(2)11-13-34)23(35)28-20-7-5-6-17-18(14-27-22(17)20)19-8-9-26-25(29-19)30-21-15-33(3)31-24(21)36-4/h5-9,14-16,27H,10-13H2,1-4H3,(H,28,35)(H,26,29,30)/t16-/m1/s1
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Summary of Clinical Use Click here for help
AZD4205 has been advanced to clinical trial to evaluate its safety and anti-tumour potential in solid and liquid tumours.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03450330 Assessing an Oral Janus Kinase Inhibitor, AZD4205, in Combination With Osimertinib in Patients Who Have Advanced Non-small Cell Lung Cancer Phase 1/Phase 2 Interventional Dizal (Jiangsu) Pharmaceutical Co., Ltd.
NCT04105010 Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8) Phase 1/Phase 2 Interventional Dizal (Jiangsu) Pharmaceutical Co., Ltd.
NCT03728023 A Study of AZD4205 in Healthy Adult Subjects Phase 1 Interventional Dizal (Jiangsu) Pharmaceutical Co., Ltd.