danicopan   Click here for help

GtoPdb Ligand ID: 11988

Synonyms: ACH-4471 | ACH4471
Compound class: Synthetic organic
Comment: Danicopan (ACH-4471) is an oral, direct inhibitor of the protease activity of complement factor D [1,4-5], which is a component of the alternative complement pathway. It was originally developed for potential to control complement-mediated intravascular hemolysis and prevent C3-mediated extravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria [3].

COVID-19: Danicoplan is being included in the ACTIV-5 platform trial NCT04988035 that is designed to identify promising agents as potential COVID-19 therapeutics that are suitable for progression to more definitive studies. It is initially being tested as a monotherapy and in combination with remdesivir in hospitalised COVID-19 patients.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 122.97
Molecular weight 579.1
XLogP 2.88
No. Lipinski's rules broken 0
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Canonical SMILES F[C@H]1CN([C@@H](C1)C(=O)Nc1cccc(n1)Br)C(=O)Cn1nc(c2c1ccc(c2)c1cnc(nc1)C)C(=O)C
Isomeric SMILES Cc1ncc(cn1)c1cc2c(cc1)n(nc2C(=O)C)CC(=O)N1C[C@@H](C[C@H]1C(=O)Nc1nc(ccc1)Br)F
InChI InChI=1S/C26H23BrFN7O3/c1-14(36)25-19-8-16(17-10-29-15(2)30-11-17)6-7-20(19)35(33-25)13-24(37)34-12-18(28)9-21(34)26(38)32-23-5-3-4-22(27)31-23/h3-8,10-11,18,21H,9,12-13H2,1-2H3,(H,31,32,38)/t18-,21+/m1/s1
1. Iyer A, Xu W, Reid RC, Fairlie DP. (2018)
Chemical Approaches to Modulating Complement-Mediated Diseases.
J Med Chem, 61 (8): 3253-3276. [PMID:28977749]
2. Kulasekararaj AG, Risitano AM, Maciejewski JP, Notaro R, Browett P, Lee JW, Huang M, Geffner M, Brodsky RA. (2021)
Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab.
Blood, 138 (20): 1928-1938. [PMID:34314483]
3. Risitano AM, Kulasekararaj AG, Lee JW, Maciejewski JP, Notaro R, Brodsky R, Huang M, Geffner M, Browett P. (2021)
Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria.
Haematologica, 106 (12): 3188-3197. [PMID:33121236]
4. Wiles JA, Galvan MD, Podos SD, Geffner M, Huang M. (2020)
Discovery and Development of the Oral Complement Factor D Inhibitor Danicopan (ACH-4471).
Curr Med Chem, 27 (25): 4165-4180. [PMID:31573880]
5. Yuan X, Gavriilaki E, Thanassi JA, Yang G, Baines AC, Podos SD, Huang Y, Huang M, Brodsky RA. (2017)
Small-molecule factor D inhibitors selectively block the alternative pathway of complement in paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.
Haematologica, 102 (3): 466-475. [PMID:27810992]