Venetoclax (ABT199)
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MedKoo CAT#: 205807

CAS#: 1257044-40-8

Description: Venetoclax, also known as ABT-199 or GDC0199, is an orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells.


Chemical Structure

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Venetoclax (ABT199)
CAS# 1257044-40-8

Theoretical Analysis

MedKoo Cat#: 205807
Name: Venetoclax (ABT199)
CAS#: 1257044-40-8
Chemical Formula: C45H50ClN7O7S
Exact Mass: 867.3181
Molecular Weight: 868.44
Elemental Analysis: C, 62.24; H, 5.80; Cl, 4.08; N, 11.29; O, 12.90; S, 3.69

Price and Availability

Size Price Availability Quantity
25.0mg USD 90.0 Ready to ship
200.0mg USD 250.0 Ready to ship
500.0mg USD 550.0 Ready to ship
1.0g USD 950.0 Ready to ship
2.0g USD 1650.0 Ready to ship
5.0g USD 3650.0 Ready to ship
10.0g USD 5750.0 Ready to ship
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Synonym: ABT199; ABT-199; ABT 199; GDC0199; GDC0199; GDC 0199; RG7601; RG7601; RG 7601. Venetoclax; Venclexta;

IUPAC/Chemical Name: 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide

InChi Key: LQBVNQSMGBZMKD-UHFFFAOYSA-N

InChi Code: InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)

SMILES Code: O=C(NS(=O)(C1=CC=C(NCC2CCOCC2)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCN(CC5=C(C6=CC=C(Cl)C=C6)CC(C)(C)CC5)CC4)C=C3OC7=CN=C(NC=C8)C8=C7

Appearance: 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

Biological target: Bcl-2 inhibitor with a Ki of less than 0.01 nM
In vitro activity: To study the selectivity of IL-VX (venetoclax-loaded immunoliposome) and to demonstrate the higher efficiency of the venetoclax-loaded liposome, the cells were also treated with free venetoclax at the same doses. Our results displayed that after 2 days of the treatment, free venetoclax did not have any apoptotic effect on CMLT1 cells even at the concentration of 1 µM, and a higher concentration was needed to observe the cytotoxic effect in this cell line (Figure 4A). However, it slightly reduced cell viability in HL60 cells. On the contrary, IL-VX induced its toxic effect on CD26+ CMLT1 cells starting from 100 nM, while its effect on CD26− HL60 cells was not significant (Figure 4B). These results confirmed the selectivity and efficiency of IL-VX and offered the opportunity to eliminate resistant cells even with a lower dose of the drug. As is clear in Figure 4C, TMRM percentage in CMLT1 was reduced following treatment with IL-VX. In healthy cells, TMRM accumulates in mitochondria and displays a bright signal. Reduction of TMRM signal may represent the reduction of mitochondria membrane potential and the start of apoptosis in treated cells. Reference: Cancers (Basel). 2021 Mar; 13(6): 1311. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000981/
In vivo activity: To address antileukemia activities of VEN (Venetoclax) in individual leukemia samples in a situation more similar to a potential clinical application, its antileukemia activities were investigated in a preclinical phase-II-like trial on different individual, patient-derived xenograft ALL samples in mice (N = 12). Three weeks after transplantation onto recipient mice, ALL-bearing animals were treated with VEN for 10 days and times to reoccurrence of full-blown, clinically apparent leukemia after treatment with VEN or vehicle were compared for each leukemia. Distinct in vivo antileukemia activities of VEN were observed and indicated by differences of survival times (‘delta survival’) ranging from minimal effects to prolonged survival without manifestation of ALL for more than 140 days (Fig.3a). This variation of in vivo responses is similar to the heterogeneity of VEN sensitivities observed ex vivo, and EC50 values analyzed ex vivo showed a moderate association with in vivo survival times (Table3,3, Supplementary Fig. 8). An analysis was then conducted to show whether the molecular markers associated with ex vivo VEN response would indicate in vivo antileukemia activity. No association of preclinical VEN activity with BCL-2 expression was found, neither alone nor relative to MCL-1 transcript levels ((Table3,3, Supplementary Fig. 8). However, direct VEN priming was associated with in vivo antileukemia activity of VEN (Table (Table33 and Fig. Fig.3b),3b), but not predictive for in vivo VEN activity (Fig.3c). Interestingly, functional dependence of the leukemia cells on BCL-2 (BAD-HRK priming) was strongly associated with in vivo VEN activity (Table33 and Fig.3d),3d), and importantly, showed high sensitivity and specificity in predicting preclinical in vivo antileukemia activity of VEN (Fig.3e3e). Reference: Cell Death Dis. 2019 Aug; 10(8): 571. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662703/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 70.0 80.6
Ethanol 0.1 0.1

Preparing Stock Solutions

The following data is based on the product molecular weight 868.44 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. Houshmand M, Garello F, Stefania R, Gaidano V, Cignetti A, Spinelli M, Fava C, Nikougoftar Zarif M, Galimberti S, Pungolino E, Annunziata M, Luciano L, Specchia G, Bocchia M, Binotto G, Bonifacio M, Martino B, Pregno P, Stagno F, Iurlo A, Russo S, Aime S, Circosta P, Saglio G. Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome. Cancers (Basel). 2021 Mar 15;13(6):1311. doi: 10.3390/cancers13061311. PMID: 33804056; PMCID: PMC8000981. 2. Seyfried F, Demir S, Hörl RL, Stirnweiß FU, Ryan J, Scheffold A, Villalobos-Ortiz M, Boldrin E, Zinngrebe J, Enzenmüller S, Jenni S, Tsai YC, Bornhauser B, Fürstberger A, Kraus JM, Kestler HA, Bourquin JP, Stilgenbauer S, Letai A, Debatin KM, Meyer LH. Prediction of venetoclax activity in precursor B-ALL by functional assessment of apoptosis signaling. Cell Death Dis. 2019 Jul 29;10(8):571. doi: 10.1038/s41419-019-1801-0. PMID: 31358732; PMCID: PMC6662703.
In vitro protocol: 1. Houshmand M, Garello F, Stefania R, Gaidano V, Cignetti A, Spinelli M, Fava C, Nikougoftar Zarif M, Galimberti S, Pungolino E, Annunziata M, Luciano L, Specchia G, Bocchia M, Binotto G, Bonifacio M, Martino B, Pregno P, Stagno F, Iurlo A, Russo S, Aime S, Circosta P, Saglio G. Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome. Cancers (Basel). 2021 Mar 15;13(6):1311. doi: 10.3390/cancers13061311. PMID: 33804056; PMCID: PMC8000981.
In vivo protocol: 1. Seyfried F, Demir S, Hörl RL, Stirnweiß FU, Ryan J, Scheffold A, Villalobos-Ortiz M, Boldrin E, Zinngrebe J, Enzenmüller S, Jenni S, Tsai YC, Bornhauser B, Fürstberger A, Kraus JM, Kestler HA, Bourquin JP, Stilgenbauer S, Letai A, Debatin KM, Meyer LH. Prediction of venetoclax activity in precursor B-ALL by functional assessment of apoptosis signaling. Cell Death Dis. 2019 Jul 29;10(8):571. doi: 10.1038/s41419-019-1801-0. PMID: 31358732; PMCID: PMC6662703.

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1. Kim MJ, Chen G, Sica GL, Deng X. Epigenetic modulation of FBW7/Mcl-1 pathway for lung cancer therapy. Cancer Biol Ther. 2021 Jan 2;22(1):55-65. doi: 10.1080/15384047.2020.1856756. Epub 2020 Dec 18. PMID: 33336620; PMCID: PMC7833779. 2.

1: Gribben JG. Practical management of tumour lysis syndrome in venetoclax-treated patients with chronic lymphocytic leukaemia. Br J Haematol. 2019 Dec 19. doi: 10.1111/bjh.16345. [Epub ahead of print] Review. PubMed PMID: 31858596.

2: Richard-Carpentier G, DiNardo CD. Venetoclax for the treatment of newly diagnosed acute myeloid leukemia in patients who are ineligible for intensive chemotherapy. Ther Adv Hematol. 2019 Oct 23;10:2040620719882822. doi: 10.1177/2040620719882822. eCollection 2019. Review. PubMed PMID: 31692757; PubMed Central PMCID: PMC6811760.

3: Juárez-Salcedo LM, Desai V, Dalia S. Venetoclax: evidence to date and clinical potential. Drugs Context. 2019 Oct 9;8:212574. doi: 10.7573/dic.212574. eCollection 2019. Review. PubMed PMID: 31645879; PubMed Central PMCID: PMC6788387.

4: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548460/ PubMed PMID: 31643779.

5: Jonas BA, Pollyea DA. How we use venetoclax with hypomethylating agents for the treatment of newly diagnosed patients with acute myeloid leukemia. Leukemia. 2019 Dec;33(12):2795-2804. doi: 10.1038/s41375-019-0612-8. Epub 2019 Oct 18. Review. PubMed PMID: 31628431.

6: Scott LJ. Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Target Oncol. 2019 Oct;14(5):493-504. doi: 10.1007/s11523-019-00673-1. Review. PubMed PMID: 31542870.

7: Eradat H. Venetoclax for the Treatment of Chronic Lymphocytic Leukemia. Curr Hematol Malig Rep. 2019 Oct;14(5):469-476. doi: 10.1007/s11899-019-00539-3. Review. PubMed PMID: 31512151.

8: Ye CJ, Xu WB, Yu Q, Wu C, Huang L, Li JM, Yan H. [Venetoclax combined with rituximab in the treatment of ibrutinib-resistant patient with chronic lymphocytic leukemia: a case report and literature reviews]. Zhonghua Xue Ye Xue Za Zhi. 2019 Aug 14;40(8):700-702. doi: 10.3760/cma.j.issn.0253-2727.2019.08.018. Review. Chinese. PubMed PMID: 31495144.

9: Seymour J. Venetoclax, the first BCL-2 inhibitor for use in patients with chronic lymphocytic leukemia. Clin Adv Hematol Oncol. 2019 Aug;17(8):440-443. Review. PubMed PMID: 31449511.

10: D'Rozario J, Bennett SK. Update on the role of venetoclax and rituximab in the treatment of relapsed or refractory CLL. Ther Adv Hematol. 2019 May 10;10:2040620719844697. doi: 10.1177/2040620719844697. eCollection 2019. Review. PubMed PMID: 31205643; PubMed Central PMCID: PMC6535706.

11: Guerra VA, DiNardo C, Konopleva M. Venetoclax-based therapies for acute myeloid leukemia. Best Pract Res Clin Haematol. 2019 Jun;32(2):145-153. doi: 10.1016/j.beha.2019.05.008. Epub 2019 May 24. Review. PubMed PMID: 31203996; PubMed Central PMCID: PMC6581210.

12: Žigart N, Časar Z. A literature review of the patent publications on venetoclax - a selective Bcl-2 inhibitor: discovering the therapeutic potential of a novel chemotherapeutic agent. Expert Opin Ther Pat. 2019 Jul;29(7):487-496. doi: 10.1080/13543776.2019.1627327. Epub 2019 Jun 7. Review. PubMed PMID: 31154862.

13: Korycka-Wolowiec A, Wolowiec D, Kubiak-Mlonka A, Robak T. Venetoclax in the treatment of chronic lymphocytic leukemia. Expert Opin Drug Metab Toxicol. 2019 May;15(5):353-366. doi: 10.1080/17425255.2019.1606211. Epub 2019 Apr 25. Review. PubMed PMID: 30969139.

14: Vaxman I, Sidiqi MH, Gertz M. Venetoclax for the treatment of multiple myeloma. Expert Rev Hematol. 2018 Dec;11(12):915-920. doi: 10.1080/17474086.2018.1548931. Epub 2018 Dec 6. Review. PubMed PMID: 30428277.

15: Leverson JD, Cojocari D. Hematologic Tumor Cell Resistance to the BCL-2 Inhibitor Venetoclax: A Product of Its Microenvironment? Front Oncol. 2018 Oct 22;8:458. doi: 10.3389/fonc.2018.00458. eCollection 2018. Review. PubMed PMID: 30406027; PubMed Central PMCID: PMC6204401.

16: Borg MA, Clemmons A. Venetoclax: A Novel Treatment for Patients With del(17p) Chronic Lymphocytic Leukemia. J Adv Pract Oncol. 2017 Sep-Oct;8(6):647-652. Epub 2017 Sep 1. Review. PubMed PMID: 30310726; PubMed Central PMCID: PMC6167086.

17: Scheffold A, Jebaraj BMC, Stilgenbauer S. Venetoclax: Targeting BCL2 in Hematological Cancers. Recent Results Cancer Res. 2018;212:215-242. doi: 10.1007/978-3-319-91439-8_11. Review. PubMed PMID: 30069633.

18: Mihalyova J, Jelinek T, Growkova K, Hrdinka M, Simicek M, Hajek R. Venetoclax: A new wave in hematooncology. Exp Hematol. 2018 May;61:10-25. doi: 10.1016/j.exphem.2018.02.002. Epub 2018 Mar 2. Review. PubMed PMID: 29477371.

19: Mistry H, Nduka C, Connock M, Colquitt J, Mantopoulos T, Loveman E, Walewska R, Mason J. Venetoclax for Treating Chronic Lymphocytic Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Pharmacoeconomics. 2018 Apr;36(4):399-406. doi: 10.1007/s40273-017-0599-9. Review. Erratum in: Pharmacoeconomics. 2019 Feb 19;:. PubMed PMID: 29222670; PubMed Central PMCID: PMC5840199.

20: Leverson JD, Sampath D, Souers AJ, Rosenberg SH, Fairbrother WJ, Amiot M, Konopleva M, Letai A. Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax. Cancer Discov. 2017 Dec;7(12):1376-1393. doi: 10.1158/2159-8290.CD-17-0797. Epub 2017 Nov 16. Review. PubMed PMID: 29146569; PubMed Central PMCID: PMC5728441.



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