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MedKoo Cat#: 200493 | Name: BI-2536
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Description:

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

BI-2563 is a small molecule compound with potential antineoplastic activities. BI 2536 binds to and inhibits Polo-like kinase 1 (Plk1), resulting in mitotic arrest, disruption of cytokinesis, and apoptosis in susceptible tumor cell populations. Plk1, a serine/threonine-protein kinase, is a key regulator of multiple processes fundamental to mitosis and cell division.

Chemical Structure

BI-2536
BI-2536
CAS#755038-02-9

Theoretical Analysis

MedKoo Cat#: 200493

Name: BI-2536

CAS#: 755038-02-9

Chemical Formula: C28H39N7O3

Exact Mass: 521.3114

Molecular Weight: 521.65

Elemental Analysis: C, 64.47; H, 7.54; N, 18.80; O, 9.20

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
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Related CAS #
No Data
Synonym
BI2536; BI-2536 BI 2536.
IUPAC/Chemical Name
(R)-4-((8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide
InChi Key
XQVVPGYIWAGRNI-JOCHJYFZSA-N
InChi Code
InChI=1S/C28H39N7O3/c1-5-22-27(37)34(3)23-17-29-28(32-25(23)35(22)20-8-6-7-9-20)31-21-11-10-18(16-24(21)38-4)26(36)30-19-12-14-33(2)15-13-19/h10-11,16-17,19-20,22H,5-9,12-15H2,1-4H3,(H,30,36)(H,29,31,32)/t22-/m1/s1
SMILES Code
O=C(NC1CCN(C)CC1)C2=CC=C(NC(N=C3N(C4CCCC4)[C@@H]5CC)=NC=C3N(C)C5=O)C(OC)=C2
Appearance
Off-white to yellow 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
>2 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
Phase I study of BI2536 in patients with advanced solid tumors. Forty-four and 26 patients received each treatment schedule, respectively. The MTD of BI 2536 in the day 1 and 8 schedule was 100 mg per administration (200 mg per course). The MTD for the second dosing schedule was not determined; a 225-mg dose was well tolerated. The most frequently reported treatment-related nonhematologic adverse events were gastrointestinal events and fatigue. Hematotoxicity as the most relevant side effect was similar in both schedules; neutropenia grades 3 and 4 were observed in 16 patients (36.4%) of the day 1 and 8 schedule and 13 patients (50%) of the 24-hour infusion. Fourteen patients (32%) treated in the day 1 and 8 dosing schedule had a best overall response of stable disease. Plasma concentrations of BI 2536 increased dose proportionally, with no relevant accumulation of exposure in the day 1 and 8 dosing schedule. The average terminal half-life was 50 hours. BI 2536 administered in either treatment schedule has adequate safety in patients with advanced solid tumors, warranting further clinical investigation of polo-like kinase-1 inhibitors. (source: Clin Cancer Res. 2010 Sep 15;16(18):4666-74 ).    BI 2536 exhibits potent activity against malignant plasma cells and represents a novel therapy in multiple myeloma .  Cells treated with BI 2536 accumulate in the G(2)/M phase of the cell cycle causing endoduplication. The effects of BI 2536 are not abrogated when cells are cultured on extracellular matrix components, in the presence of interleukin-6, or with bone marrow stromal cells. Plk1 inhibition leads to cell death in MM cell lines and patient myeloma samples. Those data suggest that inhibition of Plk1 may have potential use as a therapeutic strategy in multiple myeloma. (source: Exp Hematol. 2011 Mar;39(3):330-8 )  
Biological target:
BI 2536 is a dual PLK1 and BRD4 inhibitor with IC50s of 0.83 and 25 nM, respectively.
In vitro activity:
Exceeding a 100-fold concentration range starting at 10 nM, BI 2536 causes HeLa cells to accumulate with a 4N DNA content, indicative of a cell-cycle block in either G2 phase or mitosis. In addition to HeLa cells, BI 2536 potently inhibits the proliferation of a panel of 32 human cancer cell lines, representing diverse organ derivations (including carcinomas of the breast, colon, lung, pancreas, and prostate, melanomas, and hematopoietic cancers) and varied patterns of tumor suppressor or oncogene mutations (including RB1, TP53, PTEN, andKRAS status). The half-maximal effective concentration (EC50) values in this cell panel ranged 2-25 nM, whereas a concentration of 100 nM of BI 2536 is typically sufficient for inducing a complete mitotic arrest. The proliferation of exponentially growing hTERT-RPE1, human umbilical vein endothelial cells (HUVECs), and normal rat kidney (NRK) cells is blocked at EC50values ranging 12-31 nM, indicating a comparable sensitivity of cycling nontransformed cells to BI 2536. Reference: Curr Biol. 2007 Feb 20;17(4):316-22. https://linkinghub.elsevier.com/retrieve/pii/S0960-9822(06)02671-6
In vivo activity:
BI 2536 (40-50 mg/kg, i.v.) blocks the growth of human cancer xenografts in immunodeficient, nu/nu mice. Consecutive cycles of 40-50 mg/kg BI 2536 given i.v. once or twice per week are found to be highly efficacious in diverse xenograft models, such as the HCT 116 colon cancer with complete tumor suppression with the twice per week schedule (treated versus the control (T/C) value 0.3%) and a T/C value of 16% with once per week treatment; both schedules are well-tolerated, as judged by clinical signs and absence of major body-weight changes. Reference: Curr Biol. 2007 Feb 20;17(4):316-22. https://linkinghub.elsevier.com/retrieve/pii/S0960-9822(06)02671-6
Solvent mg/mL mM
Solubility
DMSO 65.0 124.60
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 521.65 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:
In vitro protocol:
1. Steegmaier M, Hoffmann M, Baum A, Lénárt P, Petronczki M, Krssák M, Gürtler U, Garin-Chesa P, Lieb S, Quant J, Grauert M, Adolf GR, Kraut N, Peters JM, Rettig WJ. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr Biol. 2007 Feb 20;17(4):316-22. doi: 10.1016/j.cub.2006.12.037. Epub 2007 Feb 8. PMID: 17291758. 2. Li Z, Yang C, Li X, Du X, Tao Y, Ren J, Fang F, Xie Y, Li M, Qian G, Xu L, Cao X, Wu Y, Lv H, Hu S, Lu J, Pan J. The dual role of BI 2536, a small-molecule inhibitor that targets PLK1, in induction of apoptosis and attenuation of autophagy in neuroblastoma cells. J Cancer. 2020 Mar 5;11(11):3274-3287. doi: 10.7150/jca.33110. PMID: 32231733; PMCID: PMC7097946.
In vivo protocol:
1. Steegmaier M, Hoffmann M, Baum A, Lénárt P, Petronczki M, Krssák M, Gürtler U, Garin-Chesa P, Lieb S, Quant J, Grauert M, Adolf GR, Kraut N, Peters JM, Rettig WJ. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr Biol. 2007 Feb 20;17(4):316-22. doi: 10.1016/j.cub.2006.12.037. Epub 2007 Feb 8. PMID: 17291758.
1: Müller-Tidow C, Bug G, Lübbert M, Krämer A, Krauter J, Valent P, Nachbaur D, Berdel WE, Ottmann OG, Fritsch H, Munzert G, Garin-Chesa P, Fleischer F, Taube T, Döhner H. A randomized, open-label, phase I/II trial to investigate the maximum tolerated dose of the Polo-like kinase inhibitor BI 2536 in elderly patients with refractory/relapsed acute myeloid leukaemia. Br J Haematol. 2013 Oct;163(2):214-22. doi: 10.1111/bjh.12518. Epub 2013 Aug 16. PubMed PMID: 24033250. 2: Wu CP, Hsiao SH, Sim HM, Luo SY, Tuo WC, Cheng HW, Li YQ, Huang YH, Ambudkar SV. Human ABCB1 (P-glycoprotein) and ABCG2 mediate resistance to BI 2536, a potent and selective inhibitor of Polo-like kinase 1. Biochem Pharmacol. 2013 Oct 1;86(7):904-13. doi: 10.1016/j.bcp.2013.08.004. Epub 2013 Aug 17. PubMed PMID: 23962445; PubMed Central PMCID: PMC3791609. 3: Vose JM, Friedberg JW, Waller EK, Cheson BD, Juvvigunta V, Fritsch H, Petit C, Munzert G, Younes A. The Plk1 inhibitor BI 2536 in patients with refractory or relapsed non-Hodgkin lymphoma: a phase I, open-label, single dose-escalation study. Leuk Lymphoma. 2013 Apr;54(4):708-13. doi: 10.3109/10428194.2012.729833. Epub 2012 Oct 4. PubMed PMID: 22978685. 4: Haupenthal J, Bihrer V, Korkusuz H, Kollmar O, Schmithals C, Kriener S, Engels K, Pleli T, Benz A, Canamero M, Longerich T, Kronenberger B, Richter S, Waidmann O, Vogl TJ, Zeuzem S, Piiper A. Reduced efficacy of the Plk1 inhibitor BI 2536 on the progression of hepatocellular carcinoma due to low intratumoral drug levels. Neoplasia. 2012 May;14(5):410-9. PubMed PMID: 22745587; PubMed Central PMCID: PMC3384428. 5: Mross K, Dittrich C, Aulitzky WE, Strumberg D, Schutte J, Schmid RM, Hollerbach S, Merger M, Munzert G, Fleischer F, Scheulen ME. A randomised phase II trial of the Polo-like kinase inhibitor BI 2536 in chemo-naïve patients with unresectable exocrine adenocarcinoma of the pancreas - a study within the Central European Society Anticancer Drug Research (CESAR) collaborative network. Br J Cancer. 2012 Jul 10;107(2):280-6. doi: 10.1038/bjc.2012.257. Epub 2012 Jun 14. PubMed PMID: 22699824; PubMed Central PMCID: PMC3394983. 6: Ellis PM, Chu QS, Leighl N, Laurie SA, Fritsch H, Gaschler-Markefski B, Gyorffy S, Munzert G. A phase I open-label dose-escalation study of intravenous BI 2536 together with pemetrexed in previously treated patients with non-small-cell lung cancer. Clin Lung Cancer. 2013 Jan;14(1):19-27. doi: 10.1016/j.cllc.2012.04.003. Epub 2012 Jun 1. PubMed PMID: 22658814. 7: de Oliveira JC, Brassesco MS, Pezuk JA, Morales AG, Valera ET, Montaldi AP, Sakamoto-Hojo ET, Scrideli CA, Tone LG. In vitro PLK1 inhibition by BI 2536 decreases proliferation and induces cell-cycle arrest in melanoma cells. J Drugs Dermatol. 2012 May;11(5):587-92. PubMed PMID: 22527426. 8: Frost A, Mross K, Steinbild S, Hedbom S, Unger C, Kaiser R, Trommeshauser D, Munzert G. Phase i study of the Plk1 inhibitor BI 2536 administered intravenously on three consecutive days in advanced solid tumours. Curr Oncol. 2012 Feb;19(1):e28-35. doi: 10.3747/co.19.866. PubMed PMID: 22328845; PubMed Central PMCID: PMC3267594. 9: Pezuk JA, Brassesco MS, Oliveira JC, Morales AG, Montaldi AP, Sakamoto-Hojo ET, Scrideli CA, Tone LG. Antiproliferative in vitro effects of BI 2536-mediated PLK1 inhibition on cervical adenocarcinoma cells. Clin Exp Med. 2013 Feb;13(1):75-80. doi: 10.1007/s10238-011-0166-1. Epub 2011 Nov 12. PubMed PMID: 22080235. 10: Morales AG, Brassesco MS, Pezuk JA, Oliveira JC, Montaldi AP, Sakamoto-Hojo ET, Scrideli CA, Tone LG. BI 2536-mediated PLK1 inhibition suppresses HOS and MG-63 osteosarcoma cell line growth and clonogenicity. Anticancer Drugs. 2011 Nov;22(10):995-1001. doi: 10.1097/CAD.0b013e32834a16d4. PubMed PMID: 21822121.