Padnarsertib

Padnarsertib
Clinical data
Drug class	NAMPT / PAK4 dual inhibitor
Identifiers
	IUPAC name (E)-3-(6-amino-3-pyridinyl)-N-[[5-[4-(4,4-difluoropiperidine-1-carbonyl)phenyl]-7-(4-fluorophenyl)-1-benzofuran-2-yl]methyl]prop-2-enamide;
CAS Number	1643913-93-2;
PubChem CID	117779453;
IUPHAR/BPS	10593;
DrugBank	DB19243;
ChemSpider	38772371;
UNII	9T56TV18X7;
ChEMBL	ChEMBL4297467;
Chemical and physical data
Formula	C35H29F3N4O3
Molar mass	610.637 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CN(CCC1(F)F)C(=O)C2=CC=C(C=C2)C3=CC(=C4C(=C3)C=C(O4)CNC(=O)/C=C/C5=CN=C(C=C5)N)C6=CC=C(C=C6)F;
	InChI InChI=1S/C35H29F3N4O3/c36-28-9-7-24(8-10-28)30-19-26(23-3-5-25(6-4-23)34(44)42-15-13-35(37,38)14-16-42)17-27-18-29(45-33(27)30)21-41-32(43)12-2-22-1-11-31(39)40-20-22/h1-12,17-20H,13-16,21H2,(H2,39,40)(H,41,43)/b12-2+; Key:MRFOPLWJZULAQD-SWGQDTFXSA-N;

Padnarsertib (KPT-9274), is a drug which acts as a dual inhibitor of the enzymes p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). It has potential applications in the treatment of some forms of cancer.^[1]^[2]^[3]^[4]^[5]^[6]^[7]

References

^ Abu Aboud O, Chen CH, Senapedis W, Baloglu E, Argueta C, Weiss RH (September 2016). "Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth". Molecular Cancer Therapeutics. 15 (9): 2119–2129. doi:10.1158/1535-7163.MCT-16-0197. PMC 5010932. PMID 27390344.
^ Takao S, Chien W, Madan V, Lin DC, Ding LW, Sun QY, et al. (March 2018). "Targeting the vulnerability to NAD⁺ depletion in B-cell acute lymphoblastic leukemia". Leukemia. 32 (3): 616–625. doi:10.1038/leu.2017.281. PMID 28904384.
^ Mpilla G, Aboukameel A, Muqbil I, Kim S, Beydoun R, Philip PA, et al. (November 2019). "PAK4-NAMPT Dual Inhibition as a Novel Strategy for Therapy Resistant Pancreatic Neuroendocrine Tumors". Cancers. 11 (12): 1902. doi:10.3390/cancers11121902. PMC 6966587. PMID 31795447.
^ Cordover E, Wei J, Patel C, Shan NL, Gionco J, Sargsyan D, et al. (February 2020). "KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells". Chemical Research in Toxicology. 33 (2): 482–491. doi:10.1021/acs.chemrestox.9b00376. PMC 9316853. PMID 31876149.
^ Li Y, Lu Q, Xie C, Yu Y, Zhang A (2022). "Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents". Frontiers in Pharmacology. 13 956220. doi:10.3389/fphar.2022.956220. PMC 9465411. PMID 36105226.
^ Mogol AN, Kaminsky AZ, Dutton DJ, Madak Erdogan Z (March 2024). "Targeting NAD+ Metabolism: Preclinical Insights into Potential Cancer Therapy Strategies". Endocrinology. 165 (5) bqae043. doi:10.1210/endocr/bqae043. PMID 38565429.
^ Wang Y, Minden A (September 2024). "Inhibition of NAMPT by PAK4 Inhibitors". International Journal of Molecular Sciences. 25 (18) 10138. doi:10.3390/ijms251810138. PMC 11431865. PMID 39337621.

[1] Abu Aboud O, Chen CH, Senapedis W, Baloglu E, Argueta C, Weiss RH (September 2016). "Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth". Molecular Cancer Therapeutics. 15 (9): 2119–2129. doi:10.1158/1535-7163.MCT-16-0197. PMC 5010932. PMID 27390344.

[2] Takao S, Chien W, Madan V, Lin DC, Ding LW, Sun QY, et al. (March 2018). "Targeting the vulnerability to NAD⁺ depletion in B-cell acute lymphoblastic leukemia". Leukemia. 32 (3): 616–625. doi:10.1038/leu.2017.281. PMID 28904384.

[3] Mpilla G, Aboukameel A, Muqbil I, Kim S, Beydoun R, Philip PA, et al. (November 2019). "PAK4-NAMPT Dual Inhibition as a Novel Strategy for Therapy Resistant Pancreatic Neuroendocrine Tumors". Cancers. 11 (12): 1902. doi:10.3390/cancers11121902. PMC 6966587. PMID 31795447.

[4] Cordover E, Wei J, Patel C, Shan NL, Gionco J, Sargsyan D, et al. (February 2020). "KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells". Chemical Research in Toxicology. 33 (2): 482–491. doi:10.1021/acs.chemrestox.9b00376. PMC 9316853. PMID 31876149.

[5] Li Y, Lu Q, Xie C, Yu Y, Zhang A (2022). "Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents". Frontiers in Pharmacology. 13 956220. doi:10.3389/fphar.2022.956220. PMC 9465411. PMID 36105226.

[6] Mogol AN, Kaminsky AZ, Dutton DJ, Madak Erdogan Z (March 2024). "Targeting NAD+ Metabolism: Preclinical Insights into Potential Cancer Therapy Strategies". Endocrinology. 165 (5) bqae043. doi:10.1210/endocr/bqae043. PMID 38565429.

[7] Wang Y, Minden A (September 2024). "Inhibition of NAMPT by PAK4 Inhibitors". International Journal of Molecular Sciences. 25 (18) 10138. doi:10.3390/ijms251810138. PMC 11431865. PMID 39337621.

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