A PROTAC that drives IRAK4 degradation
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KT474

Item No. 41053

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
N-[3-(difluoromethyl)-1-[trans-4-[[4-[[3-[1-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-3-methyl-2-oxo-1H-benzimidazol-4-yl]-2-propyn-1-yl]oxy]-1-piperidinyl]methyl]cyclohexyl]-1H-pyrazol-4-yl]-5-(1R,4R)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl-pyrazolo[1,5-a]pyrimidine-3-carboxamide
CAS Number
2432994-31-3
Synonyms
  • SAR444656
Molecular Formula
C44H49F2N11O6
Formula Weight
865.9
Purity
≥95%
Formulation (Request formulation change)
A solid
Solubility(Learn about Variance in Solubility)
Acetonitrile: Slightly soluble: 0.1-1 mg/mlDMSO: Sparingly soluble: 1-10 mg/ml
SMILES
O=C1N(C(CCC2=O)C(N2)=O)C3=CC=CC(C#CCOC(CC4)CCN4C[C@H]5CC[C@H](N(N=C6C(F)F)C=C6NC(C7=C(N=C(N8[C@@]9([H])CO[C@@]([H])(C8)C9)C=C%10)N%10N=C7)=O)CC5)=C3N1C
InChi Code
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
InChi Key
NQGKNAVUMAHSQN-KDRPOVOJSA-N
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    1 mg

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    Cayman Chemical
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    Product Description

    KT474 is a proteolysis-targeting chimera (PROTAC) that drives the degradation of IL-1 receptor-associated kinase 4 (IRAK4).1 It induces the degradation of IRAK4 in primary mouse and rat splenocytes and isolated dog, monkey, and human peripheral blood mononuclear cells (PBMCs) with half-maximal degradation concentration (DC50) values of 4.2, 2.1, 9.2, 2.9, and 1.5 nM, respectively. KT474 is selective for IRAK4 over a panel of 468 kinases at 1 µM. It inhibits IL-8 release induced by R-848 (Item No. 14806) in isolated human PBMCs (IC50 = 3 nM). In vivo, KT474 (30 and 100 mg/kg, p.o.) decreases ear thickness in a mouse model of psoriasis induced by imiquimod (Item No. 14956).

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Zheng, X., Ji, N., Campbell, V., et al. Discovery of KT-474─a potent, selective, and orally bioavailable IRAK4 degrader for the treatment of autoimmune diseases. J Med. Chem. 67(20), 18022-18037 (2024).