A1874

A1874 is a proteolysis-targeting chimera (PROTAC) that contains (+)-JQ1 (Cay-11187), an inhibitor of bromodomain and extra terminal domain (BET) bromodomains, conjugated to RG7388 (Cay-21532), an inhibitor of the MDM2-p53 interaction. It induces the degradation of bromodomain-containing protein 4 (BRD4), decreases the levels of c-Myc, and increases the levels of p53 and p21 in HCT116 colorectal cancer cells when used at a concentration of 10 µM. A1874 (1 µM) reduces the proliferation of wild-type p53-expressing HCT116 and A375 melanoma cells but not p53 mutant-expressing NCI H2030 lung and HT-29 colon cancer cells. It decreases cell viability and induces cell cycle arrest at the G1 phase in, and reduces colony formation by, pCAN1 colon cancer cells when used at a concentration of 500 nM. In vivo, A1874 (20 mg/kg per day) decreases tumor volume, weight, and growth in a pCAN1 mouse xenograft model.Formal Name: (6S)-N-[1-[4-[[[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)-2-pyrrolidinyl]carbonyl]amino]-3-methoxyphenyl]-1-oxo-5,8,11-trioxa-2-azatridec-13-yl]-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide. CAS Number: 2064292-12-0. Molecular Formula: C58H62Cl3F2N9O7S. Formula Weight: 1173.6. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Sparingly Soluble: 1-10 mg/ml, Ethanol: Slightly Soluble: 0.1-1 mg/ml. SMILES: O=C(C1=CC=C(NC([C@@H]2N[C@@H](CC(C)(C)C)[C@@](C3=CC=C(Cl)C=C3F)(C#N)[C@H]2C4=CC=CC(Cl)=C4F)=O)C(OC)=C1)NCCOCCOCCOCCNC(C[C@@H]5N=C(C6=C(N7C(C)=NN=C75)SC(C)=C6C)C8=CC=C(Cl)C=C8)=O. InChi Code: InChI=1S/C58H62Cl3F2N9O7S/c1-32-33(2)80-56-48(32)51(35-11-14-37(59)15-12-35)67-44(53-71-70-34(3)72(53)56)29-47(73)65-19-21-77-23-25-79-26-24-78-22-20-66-54(74)36-13-18-43(45(27-36)76-7)68-55(75)52-49(39-9-8-10-41(61)50(39)63)58(31-64,46(69-52)30-57(4,5)6)40-17-16-38(60)28-42(40)62/h8-18,27-28,44,46,49,52,69H,19-26,29-30H2,1-7H3,(H,65,73)(H,66,74)(H,68,75)/t44-,46-,49-,52+,58-/m0/s1. InChi Key: IPNTVOAQOGRLQB-JJMBTQCASA-N.