UNC2881

• CAT Number: I001839
• CAS Number: 1493764-08-1
• Molecular Formula: C25H33N7O2
• Molecular Weight: 463.58
• Purity: ≥95%
• Synonyms: 2-(butylamino)-4-[(4-hydroxycyclohexyl)amino]-N-[(4-imidazol-1-ylphenyl)methyl]pyrimidine-5-carboxamide
• InChI: InChI=1S/C25H33N7O2/c1-2-3-12-27-25-29-16-22(23(31-25)30-19-6-10-21(33)11-7-19)24(34)28-15-18-4-8-20(9-5-18)32-14-13-26-17-32/h4-5,8-9,13-14,16-17,19,21,33H,2-3,6-7,10-12,15H2,1H3,(H,28,34)(H2,27,29,30,31)
• InChIKey: NPVXOWLPOFYACO-UHFFFAOYSA-N
• SMILES: CCCCNC1=NC=C(C(=N1)NC2CCC(CC2)O)C(=O)NCC3=CC=C(C=C3)N4C=CN=C4

UNC2881 is an orally active and specific Mer kinase inhibitor, inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. UNC2881 shows additional inhibition against Axl and Tyro with IC50s of 360 nM and 250 nM, respectively. UNC2881 potently inhibits collagen-induced platelet aggregation, can be used for pathologic thrombosis research[1].
UNC2881 (compound 23) (0-1000 nM; 1 h) block ligand-stimulated activation of a chimeric EGFR-MerTK. UNC2881 also inhibits endogenous Mer tyrosine kinase activation in acute lymphoblastic leukemia cells[1].
UNC2881 (3 μM; 1 h) suppresses platelet aggregation by greater than 25% in human platelet-rich plasma in response to stimulation with fibrillar type I equine collagen[1].
UNC2881 (3 mg/kg; p.o.; single dose) has high systemic clearance (94.5 mL/min/kg) and 14% oral bioavailability, displays terminal half-life of 0.80 h[1].
UNC2881 (3 mg/kg; i.v.; injected with VSV on days -3, -2, -1, and 0) limits Mertk signaling, and promotes the antiviral immune response, reducing the viral replication of vesicular stomatitis virus (VSV) in infected mice[2].
Pharmacokinetics of UNC2881 in mice[1]

Route
Dose (mg/kg)
T1/2 (h)
Tmax (h)
Cmax (ng/mL)
AUClast (ng·h/mL)
CLobs (mL/min)
Vss (L/kg)
F (%)

IV
3
0.8

2609
527
94.5
1.65

PO
3

0.30
90.0
71.7

14

Reference

[1]. Zhang W, et al. Discovery of Mer specific tyrosine kinase inhibitors for the treatment and prevention of thrombosis. J Med Chem. 2013 Dec 12;56(23):9693-700.
 [Content Brief]

[2]. Tom Adomati, et al. Dead Cells Induce Innate Anergy Via Mertk after Acute Viral Infection. Cell Reports. 2020. 30(11):3671-3681.