Onvansertib | CAS#1034616-18-6 (free base) | PLK-1 inhibitor

MedKoo Cat#: 205779 | Name: Onvansertib free base

Description:

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

Onvansertib, also know as NMS-P937, PCM-075 and NMS1286937, is an oral Polo-like kinase 1 (PLK1) inhibitor, a key regulator of cell cycle progression and mitosis. It selectively inhibits PLK1 with a reported half-maximal inhibitory concentration (IC₅₀) of approximately 2 nM, while demonstrating significantly lower activity against other Polo-like kinases (PLK2 and PLK3). Onvansertib has shown potent anti-proliferative effects in various cancer cell lines, particularly in colorectal cancer, acute myeloid leukemia (AML), and prostate cancer models. It induces mitotic arrest, leading to apoptosis in tumor cells. Onvansertib has demonstrated synergistic effects when combined with chemotherapeutics such as irinotecan, 5-fluorouracil (5-FU), and decitabine, enhancing their efficacy in resistant cancers.

Chemical Structure

Onvansertib free base

CAS#1034616-18-6 (free base)

Theoretical Analysis

MedKoo Cat#: 205779

Name: Onvansertib free base

CAS#: 1034616-18-6 (free base)

Chemical Formula: C24H27F3N8O3

Exact Mass: 532.2158

Molecular Weight: 532.53

Elemental Analysis: C, 54.13; H, 5.11; F, 10.70; N, 21.04; O, 9.01

Price and Availability

Size	Price	Availability
10mg	USD 90.00	2 Weeks
25mg	USD 150.00	2 Weeks
50mg	USD 250.00	2 Weeks
100mg	USD 450.00	2 Weeks
1g	USD 2,950.00	2 Weeks
2g	USD 5,250.00	2 Weeks

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Related CAS #

1034616-18-6 (free base) 1263293-37-3 (fumarate)

Synonym

PCM-075; PCM 075; PCM075; NMS1286937; NMS 1286937; NMS-1286937; NMS-P937; NMS-P-937; NMS-P 937; Onvansertib

IUPAC/Chemical Name

1-(2-hydroxyethyl)-8-((5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

InChi Key

QHLVBNKYJGBCQJ-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H27F3N8O3/c1-33-6-8-34(9-7-33)15-3-5-18(38-24(25,26)27)17(12-15)30-23-29-13-14-2-4-16-20(22(28)37)32-35(10-11-36)21(16)19(14)31-23/h3,5,12-13,36H,2,4,6-11H2,1H3,(H2,28,37)(H,29,30,31)

SMILES Code

O=C(C1=NN(CCO)C2=C1CCC3=CN=C(NC4=CC(N5CCN(C)CC5)=CC=C4OC(F)(F)F)N=C23)N

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

Soluble in DMSO, not in water

Shelf Life

>5 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

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

onvansertib is an orally bioavailable, adenosine triphosphate (ATP) competitive inhibitor of polo-like kinase 1 (PLK1; PLK-1; STPK13), with potential antineoplastic activity. Upon administration, onvansertib selectively binds to and inhibits PLK1, which disrupts mitosis and induces selective G2/M cell-cycle arrest followed by apoptosis in PLK1-overexpressing tumor cells. PLK1, named after the polo gene of Drosophila melanogaster, is a serine/threonine kinase that is crucial for the regulation of mitosis, and plays a key role in tumor cell proliferation. PLK1 expression is upregulated in a variety of tumor cell types and high expression is associated with increased aggressiveness and poor prognosis

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A23O09B28

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

NMS-1286937 is a potent, selective and orally available PLK1 inhibitor, with an IC50 of 2 nM.

In vitro activity:

This prompted the study to investigate how PLK1 inhibition with the target-specific inhibitor NMS-P937 would impact breast cancer cells, and how miRNAs may influence the overall response of these cells to this inhibition. This study found that miR-183-5p targets PLK1 gene, effectively reducing its protein expression. Such miRNA-driven regulation of PLK1 expression sensitizes breast cancer cells to NMS-P937, resulting in synergistically increased apoptosis. Reference: Cell Death Differ. 2022 Feb;29(2):407-419. https://pubmed.ncbi.nlm.nih.gov/34561554/

In vivo activity:

In addition, NMS-P937 shows potential for combination in clinical settings with approved cytotoxic drugs, causing tumor regression in HT29 human colon adenocarcinoma xenografts upon combination with irinotecan and prolonged survival of animals in a disseminated model of acute myelogenous leukemia in combination with cytarabine. NMS-P937, with its favorable pharmacologic parameters, good oral bioavailability in rodent and nonrodent species, and proven antitumor activity in different preclinical models using a variety of dosing regimens, potentially provides a high degree of flexibility in dosing schedules and warrants investigation in clinical settings. Reference: Mol Cancer Ther. 2012 Apr;11(4):1006-16. https://pubmed.ncbi.nlm.nih.gov/22319201/

	Solvent	mg/mL	mM
Solubility
	DMF	5.0	9.39
	DMF:PBS (pH 7.2) (1:3)	0.3	0.47
	DMSO	12.0	22.53

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 532.53 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

Formulation protocol:

1. Kudo M, Zalles N, Distefano R, Nigita G, Veneziano D, Gasparini P, Croce CM. Synergistic apoptotic effect of miR-183-5p and Polo-Like kinase 1 inhibitor NMS-P937 in breast cancer cells. Cell Death Differ. 2022 Feb;29(2):407-419. doi: 10.1038/s41418-021-00864-2. Epub 2021 Sep 24. PMID: 34561554; PMCID: PMC8816952. 2. Sero V, Tavanti E, Vella S, Hattinger CM, Fanelli M, Michelacci F, Versteeg R, Valsasina B, Gudeman B, Picci P, Serra M. Targeting polo-like kinase 1 by NMS-P937 in osteosarcoma cell lines inhibits tumor cell growth and partially overcomes drug resistance. Invest New Drugs. 2014 Dec;32(6):1167-80. doi: 10.1007/s10637-014-0158-6. Epub 2014 Sep 7. PMID: 25193492. 3. Valsasina B, Beria I, Alli C, Alzani R, Avanzi N, Ballinari D, Cappella P, Caruso M, Casolaro A, Ciavolella A, Cucchi U, De Ponti A, Felder E, Fiorentini F, Galvani A, Gianellini LM, Giorgini ML, Isacchi A, Lansen J, Pesenti E, Rizzi S, Rocchetti M, Sola F, Moll J. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies. Mol Cancer Ther. 2012 Apr;11(4):1006-16. doi: 10.1158/1535-7163.MCT-11-0765. Epub 2012 Feb 7. PMID: 22319201. 4. Beria I, Bossi RT, Brasca MG, Caruso M, Ceccarelli W, Fachin G, Fasolini M, Forte B, Fiorentini F, Pesenti E, Pezzetta D, Posteri H, Scolaro A, Re Depaolini S, Valsasina B. NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor. Bioorg Med Chem Lett. 2011 May 15;21(10):2969-74. doi: 10.1016/j.bmcl.2011.03.054. Epub 2011 Mar 21. PMID: 21470862.

In vitro protocol:

In vivo protocol:

1. Valsasina B, Beria I, Alli C, Alzani R, Avanzi N, Ballinari D, Cappella P, Caruso M, Casolaro A, Ciavolella A, Cucchi U, De Ponti A, Felder E, Fiorentini F, Galvani A, Gianellini LM, Giorgini ML, Isacchi A, Lansen J, Pesenti E, Rizzi S, Rocchetti M, Sola F, Moll J. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies. Mol Cancer Ther. 2012 Apr;11(4):1006-16. doi: 10.1158/1535-7163.MCT-11-0765. Epub 2012 Feb 7. PMID: 22319201. 2. Beria I, Bossi RT, Brasca MG, Caruso M, Ceccarelli W, Fachin G, Fasolini M, Forte B, Fiorentini F, Pesenti E, Pezzetta D, Posteri H, Scolaro A, Re Depaolini S, Valsasina B. NMS-P937, a 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivative as potent and selective Polo-like kinase 1 inhibitor. Bioorg Med Chem Lett. 2011 May 15;21(10):2969-74. doi: 10.1016/j.bmcl.2011.03.054. Epub 2011 Mar 21. PMID: 21470862.

1: Zhang G, Pannucci A, Ivanov AA, Switchenko J, Sun SY, Sica GL, Liu Z, Huang Y, Schmitz JC, Owonikoko TK. Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer. Cancers (Basel). 2025 Jan 28;17(3):446. doi: 10.3390/cancers17030446. PMID: 39941812; PMCID: PMC11815996. 2: Petrella S, Colombo M, Marabese M, Grasselli C, Panfili A, Chiappa M, Sancisi V, Craparotta I, Barbera MC, Cassanmagnago GA, Bolis M, Damia G. Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma. Int J Mol Sci. 2025 Jan 8;26(2):472. doi: 10.3390/ijms26020472. PMID: 39859203; PMCID: PMC11765470. 3: Kim DE, Oh HJ, Kim HJ, Kim YB, Kim ST, Yim H. Synergistic two-step inhibition approach using a combination of trametinib and onvansertib in KRAS and TP53-mutated colorectal adenocarcinoma. Biomed Pharmacother. 2025 Jan;182:117796. doi: 10.1016/j.biopha.2024.117796. Epub 2024 Dec 28. PMID: 39731938. 4: Erratum: Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial. J Clin Oncol. 2025 Jan;43(1):113. doi: 10.1200/JCO-24-02458. Epub 2024 Nov 19. Erratum for: J Clin Oncol. 2025 Mar;43(7):840-851. doi: 10.1200/JCO-24-01266. PMID: 39561313. 5: Ahn DH, Ridinger M, Cannon TL, Mendelsohn L, Starr JS, Hubbard JM, Kasi A, Barzi A, Samuëlsz E, Karki A, Subramanian RA, Yemane D, Kim R, Wu CC, Croucher PJP, Smeal T, Kabbinavar FF, Lenz HJ. Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial. J Clin Oncol. 2025 Mar;43(7):840-851. doi: 10.1200/JCO-24-01266. Epub 2024 Oct 30. Erratum in: J Clin Oncol. 2025 Jan;43(1):113. doi: 10.1200/JCO-24-02458. PMID: 39475591; PMCID: PMC11856007. 6: Sreekumar S, Montaudon E, Klein D, Gonzalez ME, Painsec P, Derrien H, Sourd L, Smeal T, Marangoni E, Ridinger M. PLK1 Inhibitor Onvansertib Enhances the Efficacy of Alpelisib in PIK3CA-Mutated HR-Positive Breast Cancer Resistant to Palbociclib and Endocrine Therapy: Preclinical Insights. Cancers (Basel). 2024 Sep 25;16(19):3259. doi: 10.3390/cancers16193259. PMID: 39409880; PMCID: PMC11476299. 7: Chiappa M, Decio A, Guarrera L, Mengoli I, Karki A, Yemane D, Ghilardi C, Scanziani E, Canesi S, Barbera MC, Craparotta I, Bolis M, Fruscio R, Grasselli C, Ceruti T, Zucchetti M, Patterson JC, Lu RA, Yaffe MB, Ridinger M, Damia G, Guffanti F. Onvansertib treatment overcomes olaparib resistance in high-grade ovarian carcinomas. Cell Death Dis. 2024 Jul 22;15(7):521. doi: 10.1038/s41419-024-06894-1. PMID: 39039067; PMCID: PMC11263393. 8: Nouri M, Varkaris A, Ridinger M, Dalrymple SL, Dennehy CM, Isaacs JT, Einstein DJ, Brennen WN, Balk SP. AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer. Mol Cancer Ther. 2024 Oct 1;23(10):1404-1417. doi: 10.1158/1535-7163.MCT-23-0933. PMID: 38894678; PMCID: PMC11444904. 9: Stebbing J, Bullock AJ. Polo-like Kinase 1 Inhibition in KRAS-Mutated Metastatic Colorectal Cancer. Clin Cancer Res. 2024 May 15;30(10):2005-2007. doi: 10.1158/1078-0432.CCR-24-0251. PMID: 38470499. 10: Ahn DH, Barzi A, Ridinger M, Samuëlsz E, Subramanian RA, Croucher PJP, Smeal T, Kabbinavar FF, Lenz HJ. Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study. Clin Cancer Res. 2024 May 15;30(10):2039-2047. doi: 10.1158/1078-0432.CCR-23-3053. PMID: 38231047; PMCID: PMC11094418. 11: Croucher PJP, Ridinger M, Becker PS, Lin TL, Silberman SL, Wang ES, Zeidan AM. Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia. Ann Hematol. 2023 Nov;102(11):3049-3059. doi: 10.1007/s00277-023-05442-9. Epub 2023 Sep 13. PMID: 37702821; PMCID: PMC10567832. 12: Ansari WA, Rab SO, Saquib M, Sarfraz A, Hussain MK, Akhtar MS, Ahmad I, Khan MF. Pentafuhalol-B, a Phlorotannin from Brown Algae, Strongly Inhibits the PLK-1 Overexpression in Cancer Cells as Revealed by Computational Analysis. Molecules. 2023 Aug 3;28(15):5853. doi: 10.3390/molecules28155853. PMID: 37570823; PMCID: PMC10421442. 13: Lu J, Lei H, Bai X, Wang W, Liu C, Yang Y, Zou F, Wang L, Wang Y, Du G, Wang X, Sun C, Yu L, Ma M, Ye L, Wang H, Tian J, Zhang J. Design, synthesis, and biological evaluation of novel molecules as potent inhibitors of PLK1. Bioorg Chem. 2023 Oct;139:106711. doi: 10.1016/j.bioorg.2023.106711. Epub 2023 Jul 13. PMID: 37473479. 14: Wang R, Hou Y, Geng G, Zhu X, Wang Z, Cai W, Ye J, Zhao S, Mi Y, Jiang J. Onvansertib inhibits the proliferation and improves the cisplatin-resistance of lung adenocarcinoma via β-catenin/c-Myc signaling pathway. Am J Cancer Res. 2023 Feb 15;13(2):623-637. PMID: 36895968; PMCID: PMC9989612. 15: Patterson JC, Varkaris A, Croucher PJP, Ridinger M, Dalrymple S, Nouri M, Xie F, Varmeh S, Jonas O, Whitman MA, Chen S, Rashed S, Makusha L, Luo J, Isaacs JT, Erlander MG, Einstein DJ, Balk SP, Yaffe MB. Plk1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling. Cancer Res. 2023 Jan 18;83(2):219-238. doi: 10.1158/0008-5472.CAN-22-1533. PMID: 36413141; PMCID: PMC9852064. 16: Affatato R, Chiappa M, Guffanti F, Ricci F, Formenti L, Fruscio R, Jaconi M, Ridinger M, Erlander M, Damia G. Onvansertib and paclitaxel combined in platinum-resistant ovarian carcinomas. Ther Adv Med Oncol. 2022 May 31;14:17588359221095064. doi: 10.1177/17588359221095064. PMID: 35665077; PMCID: PMC9160919. 17: Su S, Chhabra G, Singh CK, Ndiaye MA, Ahmad N. PLK1 inhibition-based combination therapies for cancer management. Transl Oncol. 2022 Feb;16:101332. doi: 10.1016/j.tranon.2021.101332. Epub 2021 Dec 29. PMID: 34973570; PMCID: PMC8728518. 18: Hagege A, Ambrosetti D, Boyer J, Bozec A, Doyen J, Chamorey E, He X, Bourget I, Rousset J, Saada E, Rastoin O, Parola J, Luciano F, Cao Y, Pagès G, Dufies M. The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy. Theranostics. 2021 Sep 21;11(19):9571-9586. doi: 10.7150/thno.61711. PMID: 34646387; PMCID: PMC8490521. 19: Wang D, Veo B, Pierce A, Fosmire S, Madhavan K, Balakrishnan I, Donson A, Alimova I, Sullivan KD, Joshi M, Erlander M, Ridinger M, Foreman NK, Venkataraman S, Vibhakar R. A novel PLK1 inhibitor onvansertib effectively sensitizes MYC-driven medulloblastoma to radiotherapy. Neuro Oncol. 2022 Mar 12;24(3):414-426. doi: 10.1093/neuonc/noab207. PMID: 34477871; PMCID: PMC8917408. 20: Bewersdorf JP, Zeidan AM. Polo-like kinase inhibition as a therapeutic target in acute myeloid leukemia. Oncotarget. 2021 Jun 22;12(13):1314-1317. doi: 10.18632/oncotarget.27919. PMID: 34194628; PMCID: PMC8238245.