Volasertib
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MedKoo CAT#: 200494

CAS#: 755038-65-4 (free base)

Description: Volasertib, also known as BI-6727, is a dihydropteridinone Polo-like kinase 1 (Plk1) inhibitor with potential antineoplastic activity. BI 6727 selectively inhibits Plk1, inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. BI 6727 is highly potent (enzyme IC(50) = 0.87 nmol/L, EC(50) = 11-37 nmol/L on a panel of cancer cell lines) and selective dihydropteridinone with distinct properties.


Chemical Structure

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Volasertib
CAS# 755038-65-4 (free base)

Theoretical Analysis

MedKoo Cat#: 200494
Name: Volasertib
CAS#: 755038-65-4 (free base)
Chemical Formula: C34H50N8O3
Exact Mass: 618.40059
Molecular Weight: 618.81
Elemental Analysis: C, 65.99; H, 8.14; N, 18.11; O, 7.76

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 850.0 Ready to ship
200.0mg USD 1250.0 Ready to ship
500.0mg USD 1950.0 Ready to ship
1.0g USD 2950.0 Ready to ship
2.0g USD 5450.0 Ready to ship
10.0mM * 1 mL DMSO USD 250.0 Ready to ship
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Related CAS #: 946161-17-7 (HCl)   755038-65-4 (free base)    

Synonym: BI6727, BI-6727, BI 6727, Volasertib

IUPAC/Chemical Name: N-((1s,4S)-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-4-(((R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)amino)-3-methoxybenzamide

InChi Key: SXNJFOWDRLKDSF-FULLSBAXSA-N

InChi Code: InChI=1S/C34H50N8O3/c1-6-28-33(44)39(4)29-20-35-34(38-31(29)42(28)22(2)3)37-27-14-9-24(19-30(27)45-5)32(43)36-25-10-12-26(13-11-25)41-17-15-40(16-18-41)21-23-7-8-23/h9,14,19-20,22-23,25-26,28H,6-8,10-13,15-18,21H2,1-5H3,(H,36,43)(H,35,37,38)/t25-,26+,28-/m1/s1

SMILES Code: O=C(N[C@H]1CC[C@@H](N2CCN(CC3CC3)CC2)CC1)C4=CC=C(NC(N=C5N(C(C)C)[C@@H]6CC)=NC=C5N(C)C6=O)C(OC)=C4

Appearance: White to off-white 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: >3 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

Biological target: Volasertib is a highly potent Polo-like kinase 1 (PLK1) inhibitor with an IC50 of 0.87 nM, as well as the two closely related kinases PLK2 and PLK3 with IC50s of 5 and 56 nM, respectively.
In vitro activity: As Plk1 is a major regulator of mitotic cell division, the cell cycle distribution was investigated immediately after treatment with volasertib (0–20 nm, 24 h). As presented in Fig. 2A, exposure to the Plk1 inhibitor caused a significant G2/M phase block in all NSCLC cell lines (P < 0.047), accompanied by a significant decrease in number of G1 and S phase cells (both P < 0.001). The G2/M arrest was clearly influenced by the volasertib concentration (P < 0.050), the p53 status of the cell line (P < 0.001), and the oxygen tension (P < 0.001) (Table 2). Post hoc analysis revealed that the increase in % G2/M phase cells induced by higher concentrations of volasertib (12.5–20 nm) was less pronounced in p53 wild-type NSCLC cells compared to cells without functional p53, at least under normoxia. Reference: Mol Oncol. 2019 May; 13(5): 1196–1213. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487694/
In vivo activity: To investigate this further in vivo, MyLa xenografts were generated in immunodeficient mice and treated with volasertib (or vehicle control). A rapid reduction in tumor volume was observed in volasertib treated mice (Figure 2D), such that only 4 (out of 10) tumors remained observable at the time of study termination (Figure 2D, inset) in volasertib-treated mice. A significant loss of c-myc expression was observed in these tumors (Figure 2E). Reference: Oncotarget. 2017 Dec 29; 8(70): 114474–114480. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777707/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 40.0 64.64

Preparing Stock Solutions

The following data is based on the product molecular weight 618.81 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.

Recalculate based on batch purity %
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. Van den Bossche J, Deben C, De Pauw I, Lambrechts H, Hermans C, Deschoolmeester V, Jacobs J, Specenier P, Pauwels P, Vermorken JB, Peeters M, Lardon F, Wouters A. In vitro study of the Polo-like kinase 1 inhibitor volasertib in non-small-cell lung cancer reveals a role for the tumor suppressor p53. Mol Oncol. 2019 May;13(5):1196-1213. doi: 10.1002/1878-0261.12477. Epub 2019 Apr 5. PMID: 30859681; PMCID: PMC6487694. 2. Al Mamun Bhuyan A, Ashiqul Haque AKM, Sahu I, Cao H, Kormann MSD, Lang F. Inhibition of Suicidal Erythrocyte Death by Volasertib. Cell Physiol Biochem. 2017;43(4):1472-1486. doi: 10.1159/000481969. Epub 2017 Oct 16. PMID: 29035889. 3. Kats D, Ricker CA, Berlow NE, Noblet B, Nicolle D, Mevel K, Branchereau S, Judde JG, Stiverson CD, Stiverson CL, Svalina MN, Settelmeyer T, Matlock K, Lathara M, Mussini C, Geller JI, Noakes C, Sloma I, Bharathy N, Cairo S, Keller C. Volasertib preclinical activity in high-risk hepatoblastoma. Oncotarget. 2019 Nov 5;10(60):6403-6417. doi: 10.18632/oncotarget.27237. PMID: 31741706; PMCID: PMC6849653. 4. Murga-Zamalloa C, Polk A, Hanel W, Chowdhury P, Brown N, Hristov AC, Bailey NG, Wang T, Phillips T, Devata S, Poonnen P, Gomez-Gelvez J, Inamdar KV, Wilcox RA. Polo-like-kinase 1 (PLK-1) and c-myc inhibition with the dual kinase-bromodomain inhibitor volasertib in aggressive lymphomas. Oncotarget. 2017 Dec 6;8(70):114474-114480. doi: 10.18632/oncotarget.22967. PMID: 29383095; PMCID: PMC5777707.
In vitro protocol: 1. Van den Bossche J, Deben C, De Pauw I, Lambrechts H, Hermans C, Deschoolmeester V, Jacobs J, Specenier P, Pauwels P, Vermorken JB, Peeters M, Lardon F, Wouters A. In vitro study of the Polo-like kinase 1 inhibitor volasertib in non-small-cell lung cancer reveals a role for the tumor suppressor p53. Mol Oncol. 2019 May;13(5):1196-1213. doi: 10.1002/1878-0261.12477. Epub 2019 Apr 5. PMID: 30859681; PMCID: PMC6487694. 2. Al Mamun Bhuyan A, Ashiqul Haque AKM, Sahu I, Cao H, Kormann MSD, Lang F. Inhibition of Suicidal Erythrocyte Death by Volasertib. Cell Physiol Biochem. 2017;43(4):1472-1486. doi: 10.1159/000481969. Epub 2017 Oct 16. PMID: 29035889.
In vivo protocol: 1. Kats D, Ricker CA, Berlow NE, Noblet B, Nicolle D, Mevel K, Branchereau S, Judde JG, Stiverson CD, Stiverson CL, Svalina MN, Settelmeyer T, Matlock K, Lathara M, Mussini C, Geller JI, Noakes C, Sloma I, Bharathy N, Cairo S, Keller C. Volasertib preclinical activity in high-risk hepatoblastoma. Oncotarget. 2019 Nov 5;10(60):6403-6417. doi: 10.18632/oncotarget.27237. PMID: 31741706; PMCID: PMC6849653. 2. Murga-Zamalloa C, Polk A, Hanel W, Chowdhury P, Brown N, Hristov AC, Bailey NG, Wang T, Phillips T, Devata S, Poonnen P, Gomez-Gelvez J, Inamdar KV, Wilcox RA. Polo-like-kinase 1 (PLK-1) and c-myc inhibition with the dual kinase-bromodomain inhibitor volasertib in aggressive lymphomas. Oncotarget. 2017 Dec 6;8(70):114474-114480. doi: 10.18632/oncotarget.22967. PMID: 29383095; PMCID: PMC5777707.

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1: Stadler WM, Vaughn DJ, Sonpavde G, Vogelzang NJ, Tagawa ST, Petrylak DP, Rosen P, Lin CC, Mahoney J, Modi S, Lee P, Ernstoff MS, Su WC, Spira A, Pilz K, Vinisko R, Schloss C, Fritsch H, Zhao C, Carducci MA. An open-label, single-arm, phase 2 trial of the polo-like kinase inhibitor volasertib (BI 6727) in patients with locally advanced or metastatic urothelial cancer. Cancer. 2013 Dec 11. doi: 10.1002/cncr.28519. [Epub ahead of print] PubMed PMID: 24339028.

2: Danovi D, Folarin A, Gogolok S, Ender C, Elbatsh AM, Engström PG, Stricker SH, Gagrica S, Georgian A, Yu D, U KP, Harvey KJ, Ferretti P, Paddison PJ, Preston JE, Abbott NJ, Bertone P, Smith A, Pollard SM. A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1. PLoS One. 2013 Oct 30;8(10):e77053. doi: 10.1371/journal.pone.0077053. eCollection 2013. PubMed PMID: 24204733; PubMed Central PMCID: PMC3813721.

3: Gorlick R, Kolb EA, Keir ST, Maris JM, Reynolds CP, Kang MH, Carol H, Lock R, Billups CA, Kurmasheva RT, Houghton PJ, Smith MA. Initial testing (stage 1) of the Polo-like kinase inhibitor volasertib (BI 6727), by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2014 Jan;61(1):158-64. doi: 10.1002/pbc.24616. Epub 2013 Aug 19. PubMed PMID: 23956067.

4: Krause M, Kummer B, Deparade A, Eicheler W, Pfitzmann D, Yaromina A, Kunz-Schughart LA, Baumann M. Simultaneous PLK1 inhibition improves local tumour control after fractionated irradiation. Radiother Oncol. 2013 Sep;108(3):422-8. doi: 10.1016/j.radonc.2013.06.038. Epub 2013 Jul 25. PubMed PMID: 23891096.

5: Pezuk JA, Brassesco MS, Morales AG, de Oliveira JC, de Paula Queiroz RG, Machado HR, Carlotti CG Jr, Neder L, Scrideli CA, Tone LG. Polo-like kinase 1 inhibition causes decreased proliferation by cell cycle arrest, leading to cell death in glioblastoma. Cancer Gene Ther. 2013 Sep;20(9):499-506. doi: 10.1038/cgt.2013.46. Epub 2013 Jul 26. PubMed PMID: 23887645.

6: Wissing MD, Mendonca J, Kortenhorst MS, Kaelber NS, Gonzalez M, Kim E, Hammers H, van Diest PJ, Carducci MA, Kachhap SK. Targeting prostate cancer cell lines with polo-like kinase 1 inhibitors as a single agent and in combination with histone deacetylase inhibitors. FASEB J. 2013 Oct;27(10):4279-93. doi: 10.1096/fj.12-222893. Epub 2013 Jul 24. PubMed PMID: 23884428.

7: Brassesco MS, Pezuk JA, Morales AG, de Oliveira JC, Roberto GM, da Silva GN, Francisco de Oliveira H, Scrideli CA, Tone LG. In vitro targeting of Polo-like kinase 1 in bladder carcinoma: comparative effects of four potent inhibitors. Cancer Biol Ther. 2013 Jul;14(7):648-57. doi: 10.4161/cbt.25087. Epub 2013 May 31. PubMed PMID: 23792639; PubMed Central PMCID: PMC3742494.

8: Fingas CD, Mertens JC, Razumilava N, Sydor S, Bronk SF, Christensen JD, Rizvi SH, Canbay A, Treckmann JW, Paul A, Sirica AE, Gores GJ. Polo-like kinase 2 is a mediator of hedgehog survival signaling in cholangiocarcinoma. Hepatology. 2013 Oct;58(4):1362-74. doi: 10.1002/hep.26484. Epub 2013 Aug 6. PubMed PMID: 23703673; PubMed Central PMCID: PMC3811036.

9: Sanhaji M, Louwen F, Zimmer B, Kreis NN, Roth S, Yuan J. Polo-like kinase 1 inhibitors, mitotic stress and the tumor suppressor p53. Cell Cycle. 2013 May 1;12(9):1340-51. doi: 10.4161/cc.24573. Epub 2013 Apr 10. PubMed PMID: 23574746; PubMed Central PMCID: PMC3674062.

10: Kothari V, Wei I, Shankar S, Kalyana-Sundaram S, Wang L, Ma LW, Vats P, Grasso CS, Robinson DR, Wu YM, Cao X, Simeone DM, Chinnaiyan AM, Kumar-Sinha C. Outlier kinase expression by RNA sequencing as targets for precision therapy. Cancer Discov. 2013 Mar;3(3):280-93. doi: 10.1158/2159-8290.CD-12-0336. Epub 2013 Feb 5. PubMed PMID: 23384775; PubMed Central PMCID: PMC3597439.



Additional Information

Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner.