WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201270
CAS#: 170364-57-5 (free base)
Description: 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.
MedKoo Cat#: 201270
Name: Enzastaurin free base
CAS#: 170364-57-5 (free base)
Chemical Formula: C32H29N5O2
Exact Mass: 515.23213
Molecular Weight: 515.6
Elemental Analysis: C, 74.54; H, 5.67; N, 13.58; O, 6.21
Related CAS #: 170364-57-5 (free base); 359017-79-1 (HCl) 365253-37-8 (2HCl)
Synonym: LY317615; LY-317615; D04014; LY317615; DB-102; DB102; DB102; Enzastaurin; Enzastaurin free base;
IUPAC/Chemical Name: 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione
InChi Key: AXRCEOKUDYDWLF-UHFFFAOYSA-N
InChi Code: InChI=1S/C32H29N5O2/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)
SMILES Code: O=C(C(C1=CN(C)C2=C1C=CC=C2)=C3C4=CN(C5CCN(CC6=NC=CC=C6)CC5)C7=C4C=CC=C7)NC3=O
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
| Biological target: | Enzastaurin (LY317615) is a PKCβ inhibitor with an IC50 of 6 nM, showing 6- to 20-fold selectivity over PKCα, PKCγ and PKCε. |
| In vitro activity: | Enzastaurin (10(-8) -10(-6) m) potentiated aggregation of prostacyclin-washed platelets and caused an increase in VEGF release from α-granules that, in turn, promoted cancer cell survival. In platelet-rich plasma, 10(-6) m enzastaurin inhibited platelet aggregation, but not 10(-7) m enzastaurin, which also failed to suppress VEGF secretion. Reference: J Thromb Haemost. 2015 Aug;13(8):1514-20. https://pubmed.ncbi.nlm.nih.gov/25990653/ |
| In vivo activity: | A two-way ANOVA demonstrated a significant interaction [F (24,168) = 2.19, p = 0.002] and significant main effects of time [F (12, 168) = 61.86, p < 0.0001] and enzastaurin dose [F (2,14) = 8.36, p = 0.004] (Fig. 1a). In data converted to AUC, a one-way ANOVA revealed rats treated with 1 nmol enzastaurin had significantly lower levels of locomotor activity compared with vehicle treated rats [F (2,14) = 6.02, p = 0.01] (Fig. 1b). Reference: Psychopharmacology (Berl). 2019 Nov; 236(11): 3231–3242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832797/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 16.6 | 32.2 | |
| DMF:PBS (pH 7.2) (1:3) | 0.25 | 0.48 |
The following data is based on the product molecular weight 515.6 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. 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. 2. 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. 3. 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. 4. 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. |
| In vitro protocol: | 1. 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. 2. 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. |
| In vivo protocol: | 1. 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. 2. 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. |
1: Civallero M, Cosenza M, Bari A, Sacchi S. Rational combinations of enzastaurin with novel targeted agents for patients with B-cell non-Hodgkin's lymphoma. Expert Opin Investig Drugs. 2011 Aug;20(8):1029-31. Epub 2011 Jun 25. PubMed PMID: 21702717.
2: Bodo J, Sedlak J, Maciejewski JP, Almasan A, Hsi ED. HDAC inhibitors potentiate the apoptotic effect of enzastaurin in lymphoma cells. Apoptosis. 2011 Jun 11. [Epub ahead of print] PubMed PMID: 21667043.
3: Schmidinger M, Szczylik C, Sternberg CN, Kania M, Kelly CS, Decker R, Hamid O, Faelker T, Escudier B. Dose Escalation and Pharmacokinetics Study of Enzastaurin and Sunitinib Versus Placebo and Sunitinib in Patients With Metastatic Renal Cell Carcinoma. Am J Clin Oncol. 2011 Jun 4. [Epub ahead of print] PubMed PMID: 21654314.
4: Querfeld C, Kuzel TM, Kim YH, Porcu P, Duvic M, Musiek A, Rook AH, Mark LA, Pinter-Brown L, Hamid O, Lin B, Bian Y, Boye M, Day JM, Rosen ST. Multicenter phase II trial of enzastaurin in patients with relapsed or refractory advanced cutaneous T-cell lymphoma. Leuk Lymphoma. 2011 Aug;52(8):1474-80. Epub 2011 Jun 8. PubMed PMID: 21649541.
5: Ysebaert L, Morschhauser F. Enzastaurin hydrochloride for lymphoma: reassessing the results of clinical trials in light of recent advances in the biology of B-cell malignancies. Expert Opin Investig Drugs. 2011 Aug;20(8):1167-74. Epub 2011 Jun 5. PubMed PMID: 21639821.
6: Ghobrial IM, Munshi NC, Harris BN, Shi P, Porter NM, Schlossman RL, Laubach JP, Anderson KC, Desaiah D, Myrand SP, Wooldridge JE, Richardson PG, Abonour R. A phase I safety study of enzastaurin plus bortezomib in the treatment of relapsed or refractory multiple myeloma. Am J Hematol. 2011 Jul;86(7):573-8. doi: 10.1002/ajh.22048. Epub 2011 May 31. PubMed PMID: 21630305.
7: Molè D, Gagliano T, Gentilin E, Tagliati F, Pasquali C, Ambrosio MR, Pansini G, Degli Uberti EC, Zatelli MC. Targeting protein kinase C by Enzastaurin restrains proliferation and secretion in human pancreatic endocrine tumors. Endocr Relat Cancer. 2011 Jul 1;18(4):439-50. Print 2011. PubMed PMID: 21606156.
8: Rovedo MA, Krett NL, Rosen ST. Inhibition of glycogen synthase kinase-3 increases the cytotoxicity of enzastaurin. J Invest Dermatol. 2011 Jul;131(7):1442-9. doi: 10.1038/jid.2011.70. Epub 2011 Apr 7. PubMed PMID: 21471986; PubMed Central PMCID: PMC3116015.
9: Liu J, Kuo WL, Seiwert TY, Lingen M, Ciaccio MF, Jones RB, Rosner MR, Cohen EE. Effect of complementary pathway blockade on efficacy of combination enzastaurin and rapamycin. Head Neck. 2011 Mar 24. doi: 10.1002/hed.21701. [Epub ahead of print] PubMed PMID: 21438065.
10: Usha L, Sill MW, Darcy KM, Benbrook DM, Hurteau JA, Michelin DP, Mannel RS, Hanjani P, De Geest K, Godwin AK. A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies. Gynecol Oncol. 2011 Jun 1;121(3):455-61. Epub 2011 Mar 17. PubMed PMID: 21414654; PubMed Central PMCID: PMC3100412.
Enzastaurin is a synthetic 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, preventing growth.
