JNJ-1013

JNJ-1013 is a proteolysis-targeting chimera (PROTAC) containing the IL-1 receptor-associated kinase 1 (IRAK1) and IRAK4 inhibitor JH-I-25 and a methylated derivative of the PROTAC building block VH 032 (Cay-39982). It degrades IRAK1 with a half-maximal degradation concentration (DC50) value of 3.3 nM in HBL-1 diffuse large B cell lymphoma (DLBCL) cells and is selective for IRAK1 over 7,548 proteins but does degrade cyclin G-associated kinase (GAK) and NmrA-like family domain-containing protein 1 (NMRAL1) at 1 µM. JNJ-1013 (0.3-1 µM) decreases phosphorylated levels of IkappaBalpha and STAT3 in HBL-1 cells. It reduces the proliferation of HBL-1 and OCI-LY10 DLBCL cells (IC50s = 60 and 170 nM, respectively).Formal Name: N-(4-(4-(2-(((S)-1-((2S,4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-2-oxoethoxy)piperidin-1-yl)-2-methoxyphenyl)-6-(1H-pyrazol-3-yl)picolinamide. CAS Number: 2597343-08-1. Molecular Formula: C46H55N9O7S. Formula Weight: 878.1. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Slightly soluble: 0.1-1 mg/ml, DMSO: Sparingly soluble: 1-10 mg/ml, Water: Slightly soluble: 0.1-1 mg/ml. SMILES: O=C(C1=CC=CC(C2=NNC=C2)=N1)NC(C=C3)=C(OC)C=C3N4CCC(OCC(N[C@H](C(N5C[C@H](O)C[C@H]5C(N[C@@H](C)C6=CC=C(C7=C(C)N=CS7)C=C6)=O)=O)C(C)(C)C)=O)CC4. InChi Code: InChI=1S/C46H55N9O7S/c1-27(29-10-12-30(13-11-29)41-28(2)47-26-63-41)49-44(59)38-23-32(56)24-55(38)45(60)42(46(3,4)5)52-40(57)25-62-33-17-20-54(21-18-33)31-14-15-36(39(22-31)61-6)51-43(58)37-9-7-8-34(50-37)35-16-19-48-53-35/h7-16,19,22,26-27,32-33,38,42,56H,17-18,20-21,23-25H2,1-6H3,(H,48,53)(H,49,59)(H,51,58)(H,52,57)/t27-,32+,38-,42+/m0/s1. InChi Key: MHRNVFQJUUXQIG-VIFUUBRESA-N.