LC-MB12

• CAT Number: I041094
• CAS Number: 2828438-38-4
• Molecular Formula: C43H44Cl2N10O8
• Molecular Weight: 899.78
• Purity: ≥95%
• Synonyms: 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-[6-[4-[4-[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperidine-4-carbonyl]piperazin-1-yl]anilino]pyrimidin-4-yl]-1-methylurea
• InChI: InChI=1S/C43H44Cl2N10O8/c1-51(43(61)50-38-36(44)31(62-2)21-32(63-3)37(38)45)34-22-33(46-23-47-34)48-25-4-6-26(7-5-25)53-16-18-54(19-17-53)40(58)24-12-14-52(15-13-24)27-8-9-28-29(20-27)42(60)55(41(28)59)30-10-11-35(56)49-39(30)57/h4-9,20-24,30H,10-19H2,1-3H3,(H,50,61)(H,46,47,48)(H,49,56,57)
• InChIKey: BUEXWHUMUYQITQ-UHFFFAOYSA-N
• SMILES: CN(C1=NC=NC(=C1)NC2=CC=C(C=C2)N3CCN(CC3)C(=O)C4CCN(CC4)C5=CC6=C(C=C5)C(=O)N(C6=O)C7CCC(=O)NC7=O)C(=O)NC8=C(C(=CC(=C8Cl)OC)OC)Cl

LC-MB12 is an orally active PROTAC compound targets FGFR2 degradation with a DC50 of 11.8 nM. LC-MB12 contains BGJ398 (a FGFR2 inhibitor), PROTAC linker and CRBN.LC-MB12 inhibits FGFR2 signaling in gastric cancer cells and has anti-tumor activity[1].
LC-MB12 (0.5-10,000 nM, 3-12 hours) degrades FGFR2 in a time-dependent manner in KATO III, with a DC50 of 11.8 nM.
LC-MB12 (100 nM, 6 hours) degrades FGFR2 to 77% in KATO III and 43% in NCI-H1581[1].
LC-MB12 (1-10000 nM, 72 hours) inhibits the growth of KATO III, SNU-16, and NCI-H716 significantly with IC50s of 29.1 nM, 3.7 nM and 3.2 nM, respectively, and induces KATO III G0/G1 phase arrest[1].
LC-MB12 (20 mg/kg/day, p.o., 15 days) inhibits tumor growth to 63.1% in SNU-16 xenograft models of nude mice[1].
LC-MB12 (20 mg/kg, p.o.) shows fast absorption (Cmax: 2.6 h) and orally bioavailable (F: 13%) in mice[1].
LC-MB12 (20 mg/kg, p.o., 30 days) is well tolerated and has no apparent hepatotoxicity or nephrotoxicity in mice[1].

In Vivo PK Properties of LC-MB12[1]

parameter
T1/2
Tmax (ng•h/mL)
Cmax
AUC(0-∞)1/2
Vss (h)
CL
F

unit
h
h
ng/mL
h*ng/mL
mL/kg
mL/h/kg
%

iv (3 mg/kg)
0.97
0.083
655.29
421.61
6233.19
7289.12
/

po (20 mg/kg)
1.47
2.67
82.07
387.27
/
/
13.07

Reference

[1]. Ma L, et al. Discovery of a Selective and Orally Bioavailable FGFR2 Degrader for Treating Gastric Cancer. J Med Chem. 2023 Jun 8;66(11):7438-7453.
 [Content Brief]