Enzastaurin HCl | CAS# 359017-79-1 (HCl) | macrocyclic bisindolemaleimide

MedKoo Cat#: 414030 | Name: Enzastaurin HCl

Description:

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

Enzastaurin, also known as DB-102 and LY317615, is a synthetic macrocyclic bisindolemaleimide with potential antineoplastic activity. Binding to the ATP-binding site, enzastaurin selectively inhibits protein kinase C beta, an enzyme involved in the induction of vascular endothelial growth factor (VEGF)-stimulated neo-angiogenesis. This agent may decrease tumor blood supply and so tumor burden.

Chemical Structure

Enzastaurin HCl

CAS#359017-79-1 (HCl)

Theoretical Analysis

MedKoo Cat#: 414030

Name: Enzastaurin HCl

CAS#: 359017-79-1 (HCl)

Chemical Formula: C32H30ClN5O2

Exact Mass: 0.0000

Molecular Weight: 552.08

Elemental Analysis: C, 69.62; H, 5.48; Cl, 6.42; N, 12.69; O, 5.80

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.

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Related CAS #

170364-57-5 (free base) 359017-79-1 (HCl) 365253-37-8 (2HCl)

Synonym

LY317615; LY-317615; LY317615; D04014; D-04014; D 04014; DB-102; DB102; DB102; Enzastaurin; Enzastaurin HCl; Enzastaurin hydrochloride;

IUPAC/Chemical Name

3-(1-Methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione monohydrochloride

InChi Key

UUADYKVKJIMIPA-UHFFFAOYSA-N

InChi Code

InChI=1S/C32H29N5O2.ClH/c1-35-19-25(23-9-2-4-11-27(23)35)29-30(32(39)34-31(29)38)26-20-37(28-12-5-3-10-24(26)28)22-13-16-36(17-14-22)18-21-8-6-7-15-33-21;/h2-12,15,19-20,22H,13-14,16-18H2,1H3,(H,34,38,39);1H

SMILES Code

CN1C2=C(C(C(C3=O)=C(C4=CN(C5CCN(CC6=NC=CC=C6)CC5)C7=C4C=CC=C7)C(N3)=O)=C1)C=CC=C2.[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 552.08 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 ZY, Liang C, Ding M, Weng XQ, Sheng Y, Wu J, Lu H, Cai X. Enzastaurin enhances ATRA-induced differentiation of acute myeloid leukemia cells. Am J Transl Res. 2020 Dec 15;12(12):7836-7854. PMID: 33437364; PMCID: PMC7791522. 2: Nowakowski GS, Zhu J, Zhang Q, Brody J, Sun X, Maly J, Song Y, Rizvi S, Song Y, Lansigan F, Jing H, Cao J, Lue JK, Luo W, Zhang L, Li L, Han I, Sun J, Jivani M, Liu Y, Heineman T, Smith SD. ENGINE: a Phase III randomized placebo controlled study of enzastaurin/R-CHOP as frontline therapy in high-risk diffuse large B-cell lymphoma patients with the genomic biomarker DGM1. Future Oncol. 2020 May;16(15):991-999. doi: 10.2217/fon-2020-0176. Epub 2020 Apr 6. PMID: 32250167. 3: Ma G, Gezer D, Herrmann O, Feldberg K, Schemionek M, Jawhar M, Reiter A, Brümmendorf TH, Koschmieder S, Chatain N. LCP1 triggers mTORC2/AKT activity and is pharmacologically targeted by enzastaurin in hypereosinophilia. Mol Carcinog. 2020 Jan;59(1):87-103. doi: 10.1002/mc.23131. Epub 2019 Nov 6. PMID: 31691359. 4: Altshuler RD, Carpenter CA, Franke TJ, Gnegy ME, Jutkiewicz EM. Correction to: The protein kinase Cβ-selective inhibitor, enzastaurin, attenuates amphetamine-stimulated locomotor activity and self-administration behaviors in rats. Psychopharmacology (Berl). 2019 Nov;236(11):3243. doi: 10.1007/s00213-019-05312-1. Erratum for: Psychopharmacology (Berl). 2019 Nov;236(11):3231-3242. PMID: 31270556. 5: Liang C, Ding M, Weng XQ, Sheng Y, Wu J, Li ZY, Cai X. Combination of enzastaurin and ATRA exerts dose-dependent dual effects on ATRA-resistant acute promyelocytic leukemia cells. Am J Cancer Res. 2019 May 1;9(5):906-926. PMID: 31218101; PMCID: PMC6556610. 6: Altshuler RD, Carpenter CA, Franke TJ, Gnegy ME, Jutkiewicz EM. The protein kinase Cβ-selective inhibitor, enzastaurin, attenuates amphetamine-stimulated locomotor activity and self-administration behaviors in rats. Psychopharmacology (Berl). 2019 Nov;236(11):3231-3242. doi: 10.1007/s00213-019-05278-0. Epub 2019 May 27. Erratum in: Psychopharmacology (Berl). 2019 Jul 3;: PMID: 31134292; PMCID: PMC6832797. 7: He Y, Li J, Ding N, Wang X, Deng L, Xie Y, Ying Z, Liu W, Ping L, Zhang C, Song Y, Zhu J. Combination of Enzastaurin and Ibrutinib synergistically induces anti-tumor effects in diffuse large B cell lymphoma. J Exp Clin Cancer Res. 2019 Feb 18;38(1):86. doi: 10.1186/s13046-019-1076-4. PMID: 30777096; PMCID: PMC6379963. 8: Willeman MN, Mennenga SE, Siniard AL, Corneveaux JJ, De Both M, Hewitt LT, Tsang CWS, Caselli J, Braden BB, Bimonte-Nelson HA, Huentelman MJ. The PKC-β selective inhibitor, Enzastaurin, impairs memory in middle-aged rats. PLoS One. 2018 Jun 5;13(6):e0198256. doi: 10.1371/journal.pone.0198256. PMID: 29870545; PMCID: PMC5988320. 9: Steen NV, Potze L, Giovannetti E, Cavazzoni A, Ruijtenbeek R, Rolfo C, Pauwels P, Peters GJ. Molecular mechanism underlying the pharmacological interactions of the protein kinase C-β inhibitor enzastaurin and erlotinib in non-small cell lung cancer cells. Am J Cancer Res. 2017 Apr 1;7(4):816-830. PMID: 28469955; PMCID: PMC5411790. 10: Bourhill T, Narendran A, Johnston RN. Enzastaurin: A lesson in drug development. Crit Rev Oncol Hematol. 2017 Apr;112:72-79. doi: 10.1016/j.critrevonc.2017.02.003. Epub 2017 Feb 11. PMID: 28325267. 11: Crump M, Leppä S, Fayad L, Lee JJ, Di Rocco A, Ogura M, Hagberg H, Schnell F, Rifkin R, Mackensen A, Offner F, Pinter-Brown L, Smith S, Tobinai K, Yeh SP, Hsi ED, Nguyen T, Shi P, Hahka-Kemppinen M, Thornton D, Lin B, Kahl B, Schmitz N, Savage KJ, Habermann T. Randomized, Double-Blind, Phase III Trial of Enzastaurin Versus Placebo in Patients Achieving Remission After First-Line Therapy for High-Risk Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2016 Jul 20;34(21):2484-92. doi: 10.1200/JCO.2015.65.7171. Epub 2016 May 23. PMID: 27217449. 12: Li X, Fang X, Li S, Zhang W, Yang N, Cui Y, Huang H, Cai R, Lin X, Fu X, Hong H, Lin T. A pharmacokinetic and safety study of a fixed oral dose of enzastaurin HCl in native Chinese patients with refractory solid tumors and lymphoma. Oncotarget. 2016 Apr 5;7(14):18585-93. doi: 10.18632/oncotarget.7875. PMID: 26942463; PMCID: PMC4951311. 13: Odia Y, Iwamoto FM, Moustakas A, Fraum TJ, Salgado CA, Li A, Kreisl TN, Sul J, Butman JA, Fine HA. A phase II trial of enzastaurin (LY317615) in combination with bevacizumab in adults with recurrent malignant gliomas. J Neurooncol. 2016 Mar;127(1):127-35. doi: 10.1007/s11060-015-2020-x. Epub 2015 Dec 7. PMID: 26643807. 14: Welch PA, Ng WT, Darstein CL, Musib L, Lesimple T. Effects of enzastaurin and its metabolites on the QT interval in cancer patients. J Clin Pharmacol. 2016 Jan;56(1):101-8. doi: 10.1002/jcph.573. Epub 2015 Aug 17. PMID: 26096682. 15: Lesyk G, Fong T, Ruvolo PP, Jurasz P. The potential of enzastaurin to enhance platelet aggregation and growth factor secretion: implications for cancer cell survival. J Thromb Haemost. 2015 Aug;13(8):1514-20. doi: 10.1111/jth.13010. Epub 2015 Jun 17. PMID: 25990653. 16: Hainsworth JD, Arrowsmith ER, McCleod M, Hsi ED, Hamid O, Shi P, Lin BK, Fayad LE. A randomized, phase 2 study of R-CHOP plus enzastaurin vs R-CHOP in patients with intermediate- or high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2016;57(1):216-8. doi: 10.3109/10428194.2015.1045898. Epub 2015 Oct 5. PMID: 25956042. 17: Michaelis M, Rothweiler F, Löschmann N, Sharifi M, Ghafourian T, Cinatl J Jr. Enzastaurin inhibits ABCB1-mediated drug efflux independently of effects on protein kinase C signalling and the cellular p53 status. Oncotarget. 2015 Jul 10;6(19):17605-20. doi: 10.18632/oncotarget.2889. PMID: 25749379; PMCID: PMC4627332. 18: Ouaret D, Larsen AK. Protein kinase C β inhibition by enzastaurin leads to mitotic missegregation and preferential cytotoxicity toward colorectal cancer cells with chromosomal instability (CIN). Cell Cycle. 2014;13(17):2697-706. doi: 10.4161/15384101.2015.945383. PMID: 25486357; PMCID: PMC4614369. 19: Kilburn LB, Kocak M, Decker RL, Wetmore C, Chintagumpala M, Su J, Goldman S, Banerjee A, Gilbertson R, Fouladi M, Kun L, Boyett JM, Blaney SM. A phase 1 and pharmacokinetic study of enzastaurin in pediatric patients with refractory primary central nervous system tumors: a pediatric brain tumor consortium study. Neuro Oncol. 2015 Feb;17(2):303-11. doi: 10.1093/neuonc/nou114. Epub 2014 Nov 27. PMID: 25431212; PMCID: PMC4288513. 20: Cosenza M, Civallero M, Pozzi S, Marcheselli L, Bari A, Sacchi S. The combination of bortezomib with enzastaurin or lenalidomide enhances cytotoxicity in follicular and mantle cell lymphoma cell lines. Hematol Oncol. 2015 Dec;33(4):166-75. doi: 10.1002/hon.2179. Epub 2014 Nov 13. Erratum in: Hematol Oncol. 2016 Jun;34(2):117. PMID: 25394177.