PROTAC TTK degrader-1

• CAT Number: I043905
• CAS Number: 2953426-43-0
• Molecular Formula: C47H53N9O7
• Molecular Weight: 855.98
• Purity: ≥95%
• Synonyms: N-[4-[2-[4-[4-[6-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]hex-5-ynoyl]piperazin-1-yl]-2-methoxyanilino]-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8-yl]cyclohexyl]propanamide
• InChI: InChI=1S/C47H53N9O7/c1-4-40(57)49-32-11-13-33(14-12-32)56-43(60)24-29(2)36-27-48-47(52-44(36)56)50-37-17-15-34(26-39(37)63-3)53-20-22-54(23-21-53)42(59)9-7-5-6-8-30-10-16-35-31(25-30)28-55(46(35)62)38-18-19-41(58)51-45(38)61/h10,15-17,24-27,32-33,38H,4-5,7,9,11-14,18-23,28H2,1-3H3,(H,49,57)(H,48,50,52)(H,51,58,61)
• InChIKey: LWHJKWAUKAHIGC-UHFFFAOYSA-N
• SMILES: CCC(=O)NC1CCC(CC1)N2C(=O)C=C(C3=CN=C(N=C32)NC4=C(C=C(C=C4)N5CCN(CC5)C(=O)CCCC#CC6=CC7=C(C=C6)C(=O)N(C7)C8CCC(=O)NC8=O)OC)C

PROTAC TTK degrader-1 is a potent TTK (threonine tyrosine kinase) PROTAC degrader, with DC50 values of 1.7 and 5.8 nM in COLO-205 and HCT-116 cell, respectively. PROTAC TTK degrader-1 exhibits target degradation and anticancer efficacy in a xenograft mouse model of COLO-205 human colorectal cancer cells[1].
PROTAC TTK degrader-1 (compound 8e) (0-10 μM, 96 h) inhibits cancer cell proliferation[1].
PROTAC TTK degrader-1 (5 and 50 nM, 6 h) induces degradation of TTK protein in a dose-dependent manner[1].
PROTAC TTK degrader-1 (10 mg/kg, IP, single) demonstrates reasonable pharmacokinetics profiles[1].
PROTAC TTK degrader-1 (10, 20 mg/kg, IP, once daily for 16 days) significantly reduces the TTK protein levels, and exhibits tumor-growth inhibition[1].
Pharmacokinetic Parameters of PROTAC TTK degrader-1 in male SD rats[1].

8e

AUC (ng/mL*h)
2235

T1/2 (h)
4.3

Reference

[1]. Lu J, Huang Y, Huang J, et al. Discovery of the First Examples of Threonine Tyrosine Kinase PROTAC Degraders. J Med Chem. 2022;65(3):2313-2328.
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