For research use only. Not for therapeutic Use.
KT-474 (KYM-001) is an orally active PROTAC IRAK4 degrader with antitumor activities[1]. KT-474 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
KT-474 (1-100 nM) inhibits Resiquimod (HY-13740)-induced and lipopolysaccharide (HY-D1056)-induced IL-6 and IL-8 production by PBMCs[2].
KT-474 (10-100 nM) inhibits NF-kB activation (phospho-p65) in CpG-B stimulated B cells[2].
KYM-001 (48-72 h) inhibits cell cycle and induces apoptosis in ABC DLBCL, with preferential activity in MYD88-mutant vs MYD88-WT cell lines[3].
KT-474 (p.o.) induces tumor regression in xenograft models of MYD88-mutant ABC DLBCL[3].
| Catalog Number | I043444 |
| CAS Number | 2432994-31-3 |
| Synonyms | N-[3-(difluoromethyl)-1-[4-[[4-[3-[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxobenzimidazol-4-yl]prop-2-ynoxy]piperidin-1-yl]methyl]cyclohexyl]pyrazol-4-yl]-5-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide |
| Molecular Formula | C44H49F2N11O6 |
| Purity | ≥95% |
| InChI | InChI=1S/C44H49F2N11O6/c1-52-39-27(4-2-6-34(39)57(44(52)61)35-11-12-37(58)50-43(35)60)5-3-19-62-30-13-16-53(17-14-30)22-26-7-9-28(10-8-26)56-24-33(38(51-56)40(45)46)48-42(59)32-21-47-55-18-15-36(49-41(32)55)54-23-31-20-29(54)25-63-31/h2,4,6,15,18,21,24,26,28-31,35,40H,7-14,16-17,19-20,22-23,25H2,1H3,(H,48,59)(H,50,58,60)/t26?,28?,29-,31-,35?/m1/s1 |
| InChIKey | NQGKNAVUMAHSQN-PKIOHZLWSA-N |
| SMILES | CN1C2=C(C=CC=C2N(C1=O)C3CCC(=O)NC3=O)C#CCOC4CCN(CC4)CC5CCC(CC5)N6C=C(C(=N6)C(F)F)NC(=O)C7=C8N=C(C=CN8N=C7)N9CC1CC9CO1 |
| Reference | [1]. Nello Mainolfi, et al. Irak degraders and uses thereof. Patent WO2020113233A1. [2]. Ackerman L, et al. IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial. Nat Med. 2023 Dec;29(12):3127-3136. [3]. Joseph F. Kelleher, et al. Abstract LB-272: KYM-001, a first-in-class oral IRAK4 protein degrader, induces tumor regression in xenograft models of MYD88-mutant ABC DLBCL alone and in combination with BTK inhibition. Cancer Res (2019) 79 (13_Supplement): LB-272. |
