Padnarsertib HCl | CAS#1643913-93-2 | Serine/Threonine kinase inhibitor

MedKoo Cat#: 465949 | Name: Padnarsertib HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Padnarsertib, also known as KPT-9274 and PAK4-IN-1, is a potent, selective and dual PAK4/NAMPT inhibitor. KPT-9274 interferences with PAK4/NAMPT signaling pathways, which results in reduction of G2-M transit as well as induction of apoptosis and decrease in cell invasion and migration in several human RCC cell lines. Mechanistic studies demonstrate that inhibition of the PAK4 pathway by KPT-9274 attenuates nuclear β-catenin as well as the Wnt/β-catenin targets cyclin D1 and c-Myc. KPT-9274 demonstrated the expected on-target effects in this mouse model. KPT-9274 is being evaluated in a phase I human clinical trial in solid tumors and lymphomas, which will allow this data to be rapidly translated into the clinic for the treatment of RCC.

Chemical Structure

Padnarsertib HCl

CAS#Padnarsertib HCl

Theoretical Analysis

MedKoo Cat#: 465949

Name: Padnarsertib HCl

CAS#: Padnarsertib HCl

Chemical Formula: C35H31Cl2F3N4O3

Exact Mass:

Molecular Weight: 683.55

Elemental Analysis: C, 61.50; H, 4.57; Cl, 10.37; F, 8.34; N, 8.20; O, 7.02

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

Bulk Inquiry

Related CAS #

1643913-93-2 (free base) Padnarsertib HCl

Synonym

Padnarsertib HCl; KPT-9274; KPT9274; KPT 9274; PAK4-IN-1; PAK4-IN 1; PAK4-IN1;

IUPAC/Chemical Name

(E)-3-(6-aminopyridin-3-yl)-N-((5-(4-(4,4-difluoropiperidine-1-carbonyl)phenyl)-7-(4-fluorophenyl)benzofuran-2-yl)methyl)acrylamide dihydrochloride

InChi Key

HZVSZDCZEYVFLD-DIGOZPGRSA-N

InChi Code

InChI=1S/C35H29F3N4O3.2ClH/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);2*1H/b12-2+;;

SMILES Code

O=C(NCC1=CC2=CC(C3=CC=C(C(N4CCC(F)(F)CC4)=O)C=C3)=CC(C5=CC=C(F)C=C5)=C2O1)/C=C/C6=CC=C(N)N=C6.[H]Cl.[H]Cl

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 683.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

1: Li Y, Lu Q, Xie C, Yu Y, Zhang A. Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents. Front Pharmacol. 2022 Aug 29;13:956220. doi: 10.3389/fphar.2022.956220. PMID: 36105226; PMCID: PMC9465411. 2: Khan HY, Uddin MH, Balasubramanian SK, Sulaiman N, Iqbal M, Chaker M, Aboukameel A, Li Y, Senapedis W, Baloglu E, Mohammad RM, Zonder J, Azmi AS. PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma. Cancers (Basel). 2021 Dec 29;14(1):160. doi: 10.3390/cancers14010160. PMID: 35008323; PMCID: PMC8750170. 3: Subedi A, Liu Q, Ayyathan DM, Sharon D, Cathelin S, Hosseini M, Xu C, Voisin V, Bader GD, D'Alessandro A, Lechman ER, Dick JE, Minden MD, Wang JCY, Chan SM. Nicotinamide phosphoribosyltransferase inhibitors selectively induce apoptosis of AML stem cells by disrupting lipid homeostasis. Cell Stem Cell. 2021 Oct 7;28(10):1851-1867.e8. doi: 10.1016/j.stem.2021.06.004. Epub 2021 Jul 21. PMID: 34293334. 4: Sharma P, Xu J, Williams K, Easley M, Elder JB, Lonser R, Lang FF, Lapalombella R, Sampath D, Puduvalli VK. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD) salvage pathway, to target glioma heterogeneity through mitochondrial oxidative stress. Neuro Oncol. 2022 Feb 1;24(2):229-244. doi: 10.1093/neuonc/noab175. PMID: 34260721; PMCID: PMC8804900. 5: Mpilla GB, Uddin MH, Al-Hallak MN, Aboukameel A, Li Y, Kim SH, Beydoun R, Dyson G, Baloglu E, Senapedis WT, Landesman Y, Wagner KU, Viola NT, El-Rayes BF, Philip PA, Mohammad RM, Azmi AS. PAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus. Mol Cancer Ther. 2021 Oct;20(10):1836-1845. doi: 10.1158/1535-7163.MCT-20-1105. Epub 2021 Jul 12. PMID: 34253597; PMCID: PMC8492493. 6: Mitchell S, Zhang P, Cannon M, Beaver L, Lehman A, Harrington B, Sampath D, Byrd JC, Lapalombella R. Anti-tumor NAMPT inhibitor, KPT-9274, mediates gender- dependent murine anemia and nephrotoxicity by regulating SIRT3-mediated SOD deacetylation. J Hematol Oncol. 2021 Jun 29;14(1):101. doi: 10.1186/s13045-021-01107-0. PMID: 34187548; PMCID: PMC8243474. 7: Zhang P, Brinton LT, Williams K, Sher S, Orwick S, Tzung-Huei L, Mims AS, Coss CC, Kulp SK, Youssef Y, Chan WK, Mitchell S, Mustonen A, Cannon M, Phillips H, Lehman AM, Kauffman T, Beaver L, Canfield D, Grieselhuber NR, Alinari L, Sampath D, Yan P, Byrd JC, Blachly JS, Lapalombella R. Targeting DNA Damage Repair Functions of Two Histone Deacetylases, HDAC8 and SIRT6, Sensitizes Acute Myeloid Leukemia to NAMPT Inhibition. Clin Cancer Res. 2021 Apr 15;27(8):2352-2366. doi: 10.1158/1078-0432.CCR-20-3724. Epub 2021 Feb 4. PMID: 33542077; PMCID: PMC8054771. 8: Qasim SL, Sierra L, Shuck R, Kurenbekova L, Patel TD, Rajapakshe K, Wulff J, Nakahata K, Kim HR, Landesman Y, Unger TJ, Coarfa C, Yustein JT. p21-activated kinases as viable therapeutic targets for the treatment of high-risk Ewing sarcoma. Oncogene. 2021 Feb;40(6):1176-1190. doi: 10.1038/s41388-020-01600-9. Epub 2021 Jan 7. PMID: 33414491. 9: Dasgupta A, Sierra L, Tsang SV, Kurenbekova L, Patel T, Rajapakse K, Shuck RL, Rainusso N, Landesman Y, Unger T, Coarfa C, Yustein JT. Targeting PAK4 Inhibits Ras-Mediated Signaling and Multiple Oncogenic Pathways in High-Risk Rhabdomyosarcoma. Cancer Res. 2021 Jan 1;81(1):199-212. doi: 10.1158/0008-5472.CAN-20-0854. Epub 2020 Nov 9. PMID: 33168646; PMCID: PMC7878415. 10: Neggers JE, Jacquemyn M, Dierckx T, Kleinstiver BP, Thibaut HJ, Daelemans D. enAsCas12a Enables CRISPR-Directed Evolution to Screen for Functional Drug Resistance Mutations in Sequences Inaccessible to SpCas9. Mol Ther. 2021 Jan 6;29(1):208-224. doi: 10.1016/j.ymthe.2020.09.025. Epub 2020 Sep 20. PMID: 33002419; PMCID: PMC7791016. 11: Trott JF, Aboud OA, McLaughlin B, Anderson KL, Modiano JF, Kim K, Jen KY, Senapedis W, Chang H, Landesman Y, Baloglu E, Pili R, Weiss RH. Anti-Cancer Activity of PAK4/NAMPT Inhibitor and Programmed Cell Death Protein-1 Antibody in Kidney Cancer. Kidney360. 2020 May 28;1(5):376-388. doi: 10.34067/kid.0000282019. PMID: 35224510; PMCID: PMC8809296. 12: Asawa RR, Danchik C, Zakharov A, Chen Y, Voss T, Jadhav A, Wallace DP, Trott JF, Weiss RH, Simeonov A, Martinez NJ. A high-throughput screening platform for Polycystic Kidney Disease (PKD) drug repurposing utilizing murine and human ADPKD cells. Sci Rep. 2020 Mar 6;10(1):4203. doi: 10.1038/s41598-020-61082-3. Erratum in: Sci Rep. 2022 Oct 13;12(1):17185. PMID: 32144367; PMCID: PMC7060218. 13: Abril-Rodriguez G, Torrejon DY, Liu W, Zaretsky JM, Nowicki TS, Tsoi J, Puig-Saus C, Baselga-Carretero I, Medina E, Quist MJ, Garcia AJ, Senapedis W, Baloglu E, Kalbasi A, Cheung-Lau G, Berent-Maoz B, Comin-Anduix B, Hu-Lieskovan S, Wang CY, Grasso CS, Ribas A. PAK4 inhibition improves PD-1 blockade immunotherapy. Nat Cancer. 2020;1(1):46-58. doi: 10.1038/s43018-019-0003-0. Epub 2019 Dec 9. Erratum in: Nat Cancer. 2020 Feb;1(2):264. PMID: 34368780; PMCID: PMC8340852. 14: Cordover E, Wei J, Patel C, Shan NL, Gionco J, Sargsyan D, Wu R, Cai L, Kong AN, Jacinto E, Minden A. KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells. Chem Res Toxicol. 2020 Feb 17;33(2):482-491. doi: 10.1021/acs.chemrestox.9b00376. Epub 2020 Jan 9. PMID: 31876149; PMCID: PMC9316853. 15: Mpilla G, Aboukameel A, Muqbil I, Kim S, Beydoun R, Philip PA, Mohammad RM, Kamgar M, Shidham V, Senapedis W, Baloglu E, Li J, Dyson G, Xue Y, El-Rayes B, Azmi AS. PAK4-NAMPT Dual Inhibition as a Novel Strategy for Therapy Resistant Pancreatic Neuroendocrine Tumors. Cancers (Basel). 2019 Nov 29;11(12):1902. doi: 10.3390/cancers11121902. PMID: 31795447; PMCID: PMC6966587. 16: Arowosegbe MA, Amusan OT, Adeola SA, Adu OB, Akinola IA, Ogungbe BF, Omotuyi OI, Saibu GM, Ogunleye AJ, Kanmodi RI, Lugbe NE, Ogunmola OJ, Ajayi DC, Ogun SO, Oyende FO, Bello AO, Ishola PG, Obasieke PE. Kaempferol as a Potential PAK4 Inhibitor in Triple Negative Breast Cancer: Extra Precision Glide Docking and Free Energy Calculation. Curr Drug Discov Technol. 2020;17(5):682-695. doi: 10.2174/1570163816666190823135948. PMID: 31441728. 17: Mitchell SR, Larkin K, Grieselhuber NR, Lai TH, Cannon M, Orwick S, Sharma P, Asemelash Y, Zhang P, Goettl VM, Beaver L, Mims A, Puduvalli VK, Blachly JS, Lehman A, Harrington B, Henderson S, Breitbach JT, Williams KE, Dong S, Baloglu E, Senapedis W, Kirschner K, Sampath D, Lapalombella R, Byrd JC. Selective targeting of NAMPT by KPT-9274 in acute myeloid leukemia. Blood Adv. 2019 Feb 12;3(3):242-255. doi: 10.1182/bloodadvances.2018024182. PMID: 30692102; PMCID: PMC6373756. 18: Li N, Lopez MA, Linares M, Kumar S, Oliva S, Martinez-Lopez J, Xu L, Xu Y, Perini T, Senapedis W, Baloglu E, Shammas MA, Hunter Z, Anderson KC, Treon SP, Munshi NC, Fulciniti M. Dual PAK4-NAMPT Inhibition Impacts Growth and Survival, and Increases Sensitivity to DNA-Damaging Agents in Waldenström Macroglobulinemia. Clin Cancer Res. 2019 Jan 1;25(1):369-377. doi: 10.1158/1078-0432.CCR-18-1776. Epub 2018 Sep 11. PMID: 30206161; PMCID: PMC6320280. 19: Neggers JE, Kwanten B, Dierckx T, Noguchi H, Voet A, Bral L, Minner K, Massant B, Kint N, Delforge M, Vercruysse T, Baloglu E, Senapedis W, Jacquemyn M, Daelemans D. Target identification of small molecules using large-scale CRISPR-Cas mutagenesis scanning of essential genes. Nat Commun. 2018 Feb 5;9(1):502. doi: 10.1038/s41467-017-02349-8. PMID: 29402884; PMCID: PMC5799254. 20: Takao S, Chien W, Madan V, Lin DC, Ding LW, Sun QY, Mayakonda A, Sudo M, Xu L, Chen Y, Jiang YY, Gery S, Lill M, Park E, Senapedis W, Baloglu E, Müschen M, Koeffler HP. Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia. Leukemia. 2018 Mar;32(3):616-625. doi: 10.1038/leu.2017.281. Epub 2017 Sep 14. PMID: 28904384.