Venetoclax | ABT-199 | GDC-0199 | CAS#1257044-40-8 | BCL-2 Inhibitor

MedKoo Cat#: 205807 | Name: Venetoclax (ABT199)

Description:

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

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

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
25mg	USD 90.00	Ready to ship
100mg	USD 150.00	Ready to ship
200mg	USD 250.00	Ready to ship
500mg	USD 450.00	Ready to ship
1g	USD 750.00	Ready to ship
2g	USD 1,350.00	Ready to ship
5g	USD 2,950.00	Ready to ship
10g	USD 5,250.00	Ready to ship

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Related CAS #

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Synonym

ABT199; ABT-199; ABT 199; GDC0199; GDC0199; GDC 0199; RG7601; RG7601; RG 7601; Venetoclax

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

>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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A9T04K12

QC Data

View QC data: current batch, Lot#A9T04K12

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	70.0	80.60
	Ethanol	0.1	0.10

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 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.

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:

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.

1: Hu RH, Su L, Lan XX, Chang XL, Hui WH, Guo YX, Zhao H, Zhang Y, Sun WL. A retrospective assessment of real-world experience with venetoclax and azacitidine therapy in elderly acute myeloid leukemia. Anticancer Drugs. 2022 Nov 17. doi: 10.1097/CAD.0000000000001431. Epub ahead of print. PMID: 36622759. 2: Huang SM, Tao T, Wan CL, Wu TM, Cao HY, Qiu Y, Shen XD, Wang BR, Ge SS, Li YY, Zhang TT, Wu B, Xue SL. Flumatinib plus venetoclax as an effective therapy for Philadelphia chromosome-positive acute myeloid leukemia: A case report. Clin Case Rep. 2023 Jan 3;11(1):e6688. doi: 10.1002/ccr3.6688. PMID: 36619491; PMCID: PMC9810787. 3: Giudice V, Serio B, Ferrara I, Manzo P, Gorrese M, Pepe R, Bertolini A, D'Alto F, Verdesca F, Langella M, Filippelli A, Selleri C. Clinical efficacy of azacytidine and venetoclax and prognostic impact of Tim-3 and galectin-9 in acute myeloid leukemia and high-risk myelodysplastic syndromes: A single-center real-life experience. Front Pharmacol. 2022 Dec 21;13:1052060. doi: 10.3389/fphar.2022.1052060. PMID: 36618908; PMCID: PMC9810751. 4: O'Brien SM. Emerging data for venetoclax in chronic lymphocytic leukemia. Clin Adv Hematol Oncol. 2022 Mar;20(3):178-183. PMID: 36607348. 5: Tan KR, Chan YN, Iadonisi K, Poor E, Betancur S, Jung A, Sagester K, Coppola S, Pergolotti M, Kent EE, Schwartz T, Richardson D, Bryant AL. Perspectives of caregivers of older adults with acute myeloid leukemia during initial hypomethylating agents and venetoclax chemotherapy. Support Care Cancer. 2023 Jan 4;31(1):95. doi: 10.1007/s00520-022-07565-7. PMID: 36598590; PMCID: PMC9811045. 6: Hassan MA, Moukalled N, El Cheikh J, Bazarbachi A, Abou Dalle I. Azacitidine in Combination with Venetoclax Maintenance Post-allogeneic Hematopoietic Stem Cell Transplantation in T Cell Acute Lymphoblastic Leukemia. Clin Hematol Int. 2023 Jan 3. doi: 10.1007/s44228-022-00019-1. Epub ahead of print. PMID: 36595164. 7: Lasater EA, Amin DN, Bannerji R, Mali RS, Barrett K, Rys RN, Oeh J, Lin E, Sterne-Weiler T, Ingalla ER, Go M, Yu SF, Krem MM, Arthur C, Hahn U, Johnston A, Karur V, Khan N, Marlton P, Phillips T, Gritti G, Seymour JF, Tani M, Yuen S, Martin S, Chang MT, Rose CM, Pham VC, Polson AG, Chang Y, Wever C, Johnson NA, Yanwen J, Hirata J, Sampath D, Musick L, Flowers CR, Wertz IE. Targeting MCL-1 and BCL-2 with polatuzumab vedotin and venetoclax overcomes treatment resistance in R/R NHL: Results from preclinical models and a Phase Ib study. Am J Hematol. 2023 Jan 2. doi: 10.1002/ajh.26809. Epub ahead of print. PMID: 36594167. 8: Ye S, Xiong F, He X, Yuan Y, Li D, Ye D, Shi L, Lin Z, Zhao M, Feng S, Zhou B, Weng H, Hong L, Ye H, Gao S. DNA hypermethylation-induced miR-182 silence targets BCL2 and HOXA9 to facilitate the self-renewal of leukemia stem cell, accelerate acute myeloid leukemia progression, and determine the sensitivity of BCL2 inhibitor venetoclax. Theranostics. 2023 Jan 1;13(1):77-94. doi: 10.7150/thno.77404. PMID: 36593968; PMCID: PMC9800726. 9: Haselager MV, Thijssen R, Bax D, Both D, De Boer F, Mackay S, Dubois J, Mellink C, Kater AP, Eldering E. JAK-STAT signaling shapes the NF-κB response in CLL towards venetoclax sensitivity or resistance via Bcl-XL. Mol Oncol. 2022 Dec 22. doi: 10.1002/1878-0261.13364. Epub ahead of print. PMID: 36550750. 10: Dhakal P, Bates M, Tomasson MH, Sutamtewagul G, Dupuy A, Bhatt VR. Acute myeloid leukemia resistant to venetoclax-based therapy: What does the future hold? Blood Rev. 2022 Dec 1:101036. doi: 10.1016/j.blre.2022.101036. Epub ahead of print. PMID: 36549969. 11: Ramdohr F, Hennings R, Monecke A, Kayser S. Radical surgery and venetoclax + azacitidine in an octogenarian with acute myeloid leukemia. Haematologica. 2022 Dec 22. doi: 10.3324/haematol.2022.282282. Epub ahead of print. PMID: 36546450. 12: Cellini A, Scarmozzino F, Friziero A, Trimarco V, Dei Tos AP, Trentin L, Pizzi M, Visentin A. Persistent splenomegaly due to littoral cell angiomatosis in venetoclax-induced undetectable minimal residual disease of chronic lymphocytic leukemia. Ann Hematol. 2022 Dec 21. doi: 10.1007/s00277-022-05067-4. Epub ahead of print. PMID: 36542103. 13: Tsuzuki H, Kawase T, Nakazawa T, Mori M, Yoshida T. Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model. Oncotarget. 2022 Dec 20;13:1359-1368. doi: 10.18632/oncotarget.28331. PMID: 36537913; PMCID: PMC9765856. 14: Kwag D, Cho BS, Bang SY, Lee JH, Min GJ, Park SS, Park S, Yoon JH, Lee SE, Eom KS, Kim YJ, Lee S, Min CK, Cho SG, Lee JW, Kim HJ. Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis. Blood Cancer J. 2022 Dec 19;12(12):169. doi: 10.1038/s41408-022-00770-x. PMID: 36529771; PMCID: PMC9760636. 15: Teh CE, Peng H, Luo M, Tan T, Trussart M, Howson LJ, Chua CC, Muttiah C, Brown FC, Ritchie ME, Wei AH, Roberts AW, Bryant VL, Anderson MA, Lindeman GJ, Huang DCS, Thijssen R, Gray DHD. Venetoclax treatment in cancer patients has limited impact on circulating T and NK cells. Blood Adv. 2022 Dec 15:bloodadvances.2022008221. doi: 10.1182/bloodadvances.2022008221. Epub ahead of print. PMID: 36521105. 16: Gangat N, Ilyas R, McCullough K, Begna KH, Al-Kali A, Patnaik MM, Litzow MR, Hogan WJ, Mangaonkar A, Alkhateeb H, Shah MV, Elliott MA, Foran JM, Badar T, Palmer JM, Hanson CA, Pardanani A, Tefferi A. Predictors of response to venetoclax plus hypomethylating agent therapy and survival in blast-phase myeloproliferative neoplasm. Haematologica. 2022 Dec 15. doi: 10.3324/haematol.2022.282019. Epub ahead of print. PMID: 36519330. 17: Kuusanmäki H, Kytölä S, Vänttinen I, Ruokoranta T, Ranta A, Huuhtanen J, Suvela M, Parsons A, Holopainen A, Partanen A, Kuusisto MEL, Koskela S, Räty R, Itälä-Remes M, Västrik I, Dufva O, Siitonen S, Porkka K, Wennerberg K, Heckman CA, Ettala P, Pyörälä M, Rimpiläinen J, Siitonen T, Kontro M. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia. Haematologica. 2022 Dec 15. doi: 10.3324/haematol.2022.281692. Epub ahead of print. PMID: 36519325. 18: Mei C, Ye L, Ren Y, Zhou X, Ma L, Xu G, Xu W, Lu C, Yang H, Luo Y, Jiang L, Lang W, Zhu H, Jin J, Tong H. 15-days duration of Venetoclax combined with azacitidine in the treatment of relapsed/refractory high-risk myelodysplastic syndromes: A retrospective single-center study. Hematol Oncol. 2022 Dec 14. doi: 10.1002/hon.3112. Epub ahead of print. PMID: 36516239. 19: Kuusanmäki H, Dufva O, Vähä-Koskela M, Leppä AM, Huuhtanen J, Vänttinen IM, Nygren PJ, Klievink J, Bouhlal JOV, Pölönen P, Zhang Q, Adnan Awad S, Mancebo- Pérez C, Saad J, Miettinen JJ, Javarappa KK, Aakko S, Ruokoranta T, Eldfors S, Heinäniemi M, Theilgaard-Mönch K, Wartiovaara-Kautto U, Keränen MAI, Porkka K, Konopleva M, Wennerberg K, Kontro M, Heckman CA, Mustjoki S. Erythroid/megakaryocytic differentiation confers BCL-XL dependency and venetoclax resistance in acute myeloid leukemia. Blood. 2022 Dec 12:blood.2021011094. doi: 10.1182/blood.2021011094. Epub ahead of print. PMID: 36508699. 20: Scarfò L. Novel therapies and combinations in CLL refractory to BTK inhibitors and venetoclax. Hematology Am Soc Hematol Educ Program. 2022 Dec 9;2022(1):316-322. doi: 10.1182/hematology.2022000344. PMID: 36485153; PMCID: PMC9820511.

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