| Identification | Back Directory | [Name]
1-((2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one | [CAS]
1792180-81-4 | [Synonyms]
CS-2733
EOS-61890
PF-06651600
Ritlecitinib
PF-06651600;PF 06651600;PF06651600
1-((2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2
1-((2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one
2-Propen-1-one, 1-[(2S,5R)-2-methyl-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1-piperidinyl]-
1-[(2S,5R)-2-methyl-5(7H-pyrrolo[2,3-d]pyrimidine-4-ylamino)-1-piperidinly]-2-propen-1-one malonate,PF06651600 | [EINECS(EC#)]
210-077-2 | [Molecular Formula]
C15H19N5O | [MDL Number]
MFCD31697544 | [MOL File]
1792180-81-4.mol | [Molecular Weight]
285.34 |
| Chemical Properties | Back Directory | [density ]
1.272±0.06 g/cm3(Predicted) | [storage temp. ]
room temp | [solubility ]
DMSO:100.0(Max Conc. mg/mL);350.4(Max Conc. mM)
H2O:5.0(Max Conc. mg/mL);17.5(Max Conc. mM) | [form ]
powder | [pka]
13.03±0.50(Predicted) | [color ]
white to beige | [InChI]
InChI=1S/C15H19N5O/c1-3-13(21)20-8-11(5-4-10(20)2)19-15-12-6-7-16-14(12)17-9-18-15/h3,6-7,9-11H,1,4-5,8H2,2H3,(H2,16,17,18,19)/t10-,11+/m0/s1 | [InChIKey]
CBRJPFGIXUFMTM-WDEREUQCSA-N | [SMILES]
C(N1C[C@H](NC2N=CN=C3NC=CC3=2)CC[C@@H]1C)(=O)C=C |
| Hazard Information | Back Directory | [Description]
Ritlecitinib, a dual JAK3/TEC inhibitor, was granted FDA breakthrough status for treating alopecia areata (autoimmune-induced hair loss) in September 2018. Promising phase 3 trial results in alopecia areata were reported by Pfizer in August 2021, placing it in competition with Lilly/Incyte’s Olumiant. It is also used in clinical studies to treat vitiligo, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis. Ritlecitinib achieved high JAK3 selectivity via covalent interaction with a unique cysteine residue (Cys909) in the catalytic domain.
| [Characteristics]
Primary targets: JAK3/TEC
Class: non-receptor tyrosine kinase
Treatment: alopecia areata (phase III)
Protein binding = 14%
| [Biochem/physiol Actions]
PF-06651600 is a potent and selective JAK3 inhibitor. | [Pharmacokinetics]
Ritlecitinib exhibited low clearance in rats and dogs, contributing to its good oral bioavailability (85% in rats and 109% in dogs). Its lower oral bioavailability in monkeys (56%) primarily resulted from its fast clearance. The pharmacokinetic properties are directly linked to its stability in hepatocytes and whole blood, demonstrating the power of in vitro assays to predict in vivo pharmacokinetic parameters. The good oral bioavailability obtained from rats and dogs was a combination of high passive permeability, high aqueous solubility (>2 mg/mL), and low hepatic clearance. Ritlecitinib underwent CYP3A4-mediated oxidation of the acrylamide and piperidine ring and glutathione conjugated with the acrylamide. Allometric scaling predicted an oral bioavailability of 90% and a half-life of 2 h in humans, which need to be verified in clinical trials.
| [storage]
Store at -20°C |
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