Cat. No.: HY-129179

Lisaftoclax

Name: Lisaftoclax
Brand: MedChemExpress
SKU: HY-129179
Price: 380.00 USD
Availability: InStock
Rating: 5 (1 reviews)

(Synonyms: APG-2575; Bcl-2/Bcl-xl inhibitor 1)

1 Cited Publications

Customer Review

Based on 1 publication(s) in Google Scholar

Lisaftoclax is an orally active, selective BCL-2 inhibitor with a K_i of < 0.1 nM against human BCL-2. Lisaftoclax selectively binds to BCL-2, disrupts the BCL-2:BIM complex, and antagonizes the antiapoptotic function of BCL-2. Lisaftoclax induces BAX/BAK-dependent, caspase-mediated apoptosis, upregulates the pro-death proteins BIM and Noxa, and downregulates mitochondrial respiratory function and ATP production. Lisaftoclax can be used in the research of hematological malignancies including chronic lymphocytic leukemia, multiple myeloma, and diffuse large B-cell lymphoma.

For research use only. We do not sell to patients.

Purity: 99.78%
CAS No.: 2180923-05-9
Formula: C₄₅H₄₈ClN₇O₈S
Molecular Weight:882.42

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Lisaftoclax Chemical Structure

CAS No.: 2180923-05-9

Size

Price

Stock

Quantity

Amount: USD 0.00

* Please select Quantity before adding items.

Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
- Clinical Trial
Chemical Information
Publications (1)
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[1]^[2]^[3]^[4]^[5]

Bcl-2

Bcl-xL

All Bcl-2 Family Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
RS4-11	IC₅₀	161 nM Compound: 3; APG-2575	Inhibition of cell growth in human RS4-11 cells harboring Bcl-2 G101V mutant incubated for 2 days by CellTiter-Glo luminescent cell viability assay Inhibition of cell growth in human RS4-11 cells harboring Bcl-2 G101V mutant incubated for 2 days by CellTiter-Glo luminescent cell viability assay	[PMID: 38695063]
RS4-11	IC₅₀	6.3 nM Compound: 3; APG-2575	Inhibition of cell growth in human RS4-11 cells incubated for 2 days by CellTiter-Glo luminescent cell viability assay Inhibition of cell growth in human RS4-11 cells incubated for 2 days by CellTiter-Glo luminescent cell viability assay	[PMID: 38695063]

In Vitro

Lisaftoclax (serial dilution; 2 h) potently and selectively binds to recombinant human BCL-2 with a K_i < 0.1 nM, while it shows weak affinity for BCL-xL and MCL-1^[2].
Lisaftoclax (serial dilution; 4 days) exerts no significant inhibitory effect on the viability of BCL-xL-dependent SKLU-1 cells or MCL-1-dependent NCI-H23 cells^[2].
Lisaftoclax (serial dilution; 4 days) potently inhibits the viability of BCL-2-dependent RS4;11, HL-60 and MV-4-11 cells, with IC₅₀ values of 3.6 nM, 2.4 nM and 1.9 nM, respectively^[2].
Lisaftoclax (serial dilution; 4 h treatment) inhibits the viability of primary CD19⁺/CD5⁺ B cells derived from patients with chronic lymphocytic leukemia (CLL)^[2].
Lisaftoclax (serial dilution; 3 days) potently inhibits the viability of MM and WM cell lines as well as primary human MM cells, with median IC₅₀ values of 3.6 µM (MM cell lines), 3.0 µM (WM cell lines) and 1.33 µM (primary MM cells)^[2].
Lisaftoclax potently inhibits the viability of RS4;11 leukemia cells, with an IC₅₀ of 5.5 nM^[5].
Lisaftoclax potently inhibits the activity of Molm13 leukemia cells, with an IC₅₀ of 6.4 nM^[5].
Lisaftoclax (30-50 nM, 0.1-1 μM; 1-24 h) selectively disrupts the BCL-2:BIM complex in a dose- and time-dependent manner in RS4;11, Toledo, SU-DHL-4, KMS-11 and BCWM.1 cells, and this complex disruption occurs concomitantly with increased apoptosis levels in RS4;11 cells^[2].
Lisaftoclax (serial gradient dilution; 24 h) induces cytochrome c release and apoptosis in BCL-2-overexpressing O-BCL-2 cells in a BAX/BAK-dependent manner, while exhibits extremely low activity in cells overexpressing BCL-xL, MCL-1 or BFL-1/A1^[2].
Lisaftoclax (1 μM; 24 hours) activates caspase-3/7 levels in multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) cell lines^[2].
Lisaftoclax (1 μM; 3 days) induces apoptosis in tumor cells derived from patients with primary multiple myeloma (MM) and Waldenström's macroglobulinemia (WM)^[2].
Lisaftoclax (1 μM; 0.5-6 hours) rapidly upregulates the expression levels of pro-apoptotic proteins BIM and Noxa, and promotes the translocation of BIM to mitochondria in KMS-11 and BCWM.1 cells following treatment with 1 μM lisaftoclax for up to 6 hours^[2].
Lisaftoclax (1 μM; 24 h) significantly impairs mitochondrial bioenergetic function in KMS-11 cells. Treatment with 1 μM Lisaftoclax for 24 h reduces the maximal respiratory rate, non-mitochondrial respiratory rate, spare respiratory capacity, and mitochondrial ATP production of the cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[2]

Cell Line:

BCL-2-dependent cell lines (RS4;11, HL-60, MV-4-11)
Concentration:

Serial dilutions
Incubation Time:

4 days
Result:

Inhibited cell viability with IC₅₀ values of 3.6 nM in RS4;11 cells, 2.4 nM in HL-60 cells, and 1.9 nM in MV-4-11 cells.

Cell Viability Assay^[2]

Cell Line:

BCL-xL-dependent SKLU-1 cells, MCL-1-dependent NCI-H23 cells
Concentration:

Serial dilutions
Incubation Time:

4 days
Result:

Showed minimal effects on cell viability in BCL-xL-dependent SKLU-1 cells and no effect on viability in MCL-1-dependent NCI-H23 cells.

Cell Proliferation Assay^[2]

Cell Line:

Multiple myeloma (MM) cell lines, Waldenström macroglobulinemia (WM) cell lines, primary human MM cells
Concentration:

Serial dilutions
Incubation Time:

3 days
Result:

In MM cell lines, the median IC₅₀ was 3.6 µM; in WM cell lines, the median IC₅₀ was 3.0 µM.
In primary human MM cells, the median IC₅₀ was 1.33 µM, which was ≥2 times lower than venetoclax's median IC₅₀ of 3.01 µM.

Apoptosis Analysis^[2]

Cell Line:

Engineered cell lines (O-BCL-2, O-BCL-xL, O-MCL-1, O-BFL-1/A1, O-DKO [BAX/BAK double knockout])
Concentration:

Serial dilutions
Incubation Time:

24 h
Result:

Induced cytochrome c release from O-BCL-2 mitochondria at a concentration 2 orders of magnitude lower than in O-BCL-xL mitochondria, with no effect on O-MCL-1 or O-BFL-1/A1 mitochondria.
Induced apoptosis in O-BCL-2 cells but not in O-BCL-xL, O-MCL-1, O-BFL-1/A1, or O-DKO cells.

Western Blot Analysis^[2]

Cell Line:

KMS-11, BCWM.1 cell lines
Concentration:

1 μM
Incubation Time:

0.5, 1, 2, 6 hours (Western Blot); 4 hours (Immunofluorescence)
Result:

Significantly increased BIM levels within 2 hours and Noxa levels within 1-6 hours.
More BIM accumulated in mitochondria of KMS-11 cells after treatment compared to vehicle or Venetoclax (HY-15531).

Parmacokinetics

Species	Dose	Route	T_max	C_max	AUC_0-t	AUC_0-∞	T_1/2	CL	V_ss	MRT_{INF_obs}
Rat^[5]	2 mg/kg	i.v.	0.083 h	4174 ng/mL	2899 ng·h/mL	2915 ng·h/mL	4.39 h	0.695 L/h/kg	1.44 L/kg	2.09 h
Rat^[5]	20 mg/kg	p.o.	2.67 h	2623 ng/mL	13424 ng·h/mL	13475 ng·h/mL	3.12 h	/	/	/

In Vivo

Lisaftoclax (3.125-100 mg/kg; p.o.; once daily; 15 days) exhibits dose-dependent antitumor activity in the RS4;11 acute lymphoblastic leukemia xenograft model, achieves a maximum tumor growth inhibition rate (T/C 4%) at a daily oral dose of 100 mg/kg, and induces apoptosis via cleavage of caspase-3 and PARP-1^[2].
Lisaftoclax (100 mg/kg; p.o.; once daily; for 15 consecutive days) significantly reduces tumor burden and prolongs survival in the KMS-11 multiple myeloma xenograft model, with enhanced apoptotic effects indicated by increased levels of activated caspase-3^[2].
Lisaftoclax (100 mg/kg; p.o.; daily) inhibits tumor growth and prolongs survival in the BCWM.1 Waldenström's macroglobulinemia xenograft model, and its pro-apoptotic effect is confirmed by elevated levels of activated caspase-3^[2].
Lisaftoclax (25-100 mg/kg; p.o.; daily) exhibits dose-dependent antitumor activity in the Toledo diffuse large B-cell lymphoma xenograft model, with the strongest inhibitory effect observed at the daily oral dose of 100 mg/kg^[2].
Combination treatment with Lisaftoclax (100 mg/kg; p.o.; daily; monotherapy for 15 days, combined with Bendamustine (HY-13567) and Rituximab (HY-P9913) for 35 days), Bendamustine and Rituximab induces sustained complete tumor regression in the OCI-LY8 diffuse large B-cell lymphoma xenograft model, with superior efficacy compared to Lisaftoclax monotherapy and the BR dual-drug combination regimen^[2].
Lisaftoclax (100 mg/kg; p.o.; once daily; for 29 consecutive days) exhibits anti-tumor activity and prolongs survival in an Ibrutinib (HY-10997)-resistant patient-derived xenograft model of Waldenström's macroglobulinemia^[2].
Lisaftoclax (p.o.) exhibits in vivo anti-tumor activity against RS4;11 leukemia xenografts in nude mice without inducing body weight loss^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

NOD/SCID or NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (male, 6-8 weeks old)^[2]
Dosage:

3.125 mg/kg; 6.25 mg/kg; 12.5 mg/kg; 25 mg/kg; 50 mg/kg; 100 mg/kg
Administration:

p.o.; daily; 15 days
Result:

Achieved a treatment/control (T/C) ratio of 60% with 6.25 mg/kg dose by Day 15.
Achieved a T/C ratio of 4% with 100 mg/kg dose by Day 15.
Induced no significant body weight changes with any dose.
Triggered cleaved caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1) cleavage in tumor tissue with a single 6.25 mg/kg oral dose, with peak activity at 24 hours post-dose.

Animal Model:

NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (male, 6-8 weeks old)^[2]
Dosage:

25 mg/kg; 50 mg/kg; 100 mg/kg
Administration:

p.o.; daily
Result:

Exhibited dose-proportional tumor growth inhibition, with the greatest inhibition observed at the 100 mg/kg daily dose.

Animal Model:

NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ)^[2]
Dosage:

100 mg/kg (single agent); 100 mg/kg (combined with bendamustine and rituximab)
Administration:

p.o.; daily; 15 days (single agent); p.o.; daily; 35 days (combined with bendamustine and rituximab)
Result:

Induced sustained tumor regression with 100% complete response (6/6 mice) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) when combined with bendamustine and rituximab.
Demonstrated superior antitumor effects compared to lisaftoclax alone or the bendamustine and rituximab (BR) dual combination.

Animal Model:

NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (10 per group)^[2]
Dosage:

100 mg/kg
Administration:

p.o.; daily; 15 days
Result:

Significantly reduced tumor burden (total flux; P = 0.0010 vs vehicle) by Day 20.
Prolonged median survival to 25 days compared to vehicle control (21 days; P < 0.0500).
Increased cleaved caspase-3 staining intensity in tumors (P = 0.0220 vs vehicle).
Decreased Ki67 staining in tumors.
Induced no significant body weight loss.

Animal Model:

NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ)^[2]
Dosage:

100 mg/kg
Administration:

p.o.; daily
Result:

Achieved a T/C ratio of 25.12% by Day 15 with no apparent toxicity or weight loss.
Prolonged median survival to 29 days compared to vehicle (21 days; P = 0.0190).
Increased cleaved caspase-3 staining intensity in tumors (P = 0.0025 vs vehicle).

Animal Model:

NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) (male, 6-8 weeks old, 8 per group)^[2]
Dosage:

100 mg/kg
Administration:

p.o.; daily; 29 days
Result:

Resulted in significantly lower tumor burden (T/C 17.56%) compared to venetoclax (P = 0.0002) or ibrutinib (P = 0.0003).
Prolonged median survival to 63 days compared to venetoclax (36 days; P = 0.002), vehicle (34 days), or ibrutinib (38 days).

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 2180923-05-9
Appearance Solid
Molecular Weight 882.42
Formula C₄₅H₄₈ClN₇O₈S
Color Light yellow to yellow
SMILES

O=C(NS(=O)(C1=CC=C(NC[C@@H]2OCCOC2)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCN(CC(CC5)=C(C6=CC=C(Cl)C=C6)CC75CCC7)CC4)C=C3OC8=CN=C(NC=C9)C9=C8
Synonyms

APG-2575; Bcl-2/Bcl-xl inhibitor 1
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (1)

All

Sort by:

Journal Impact Factor

Cell Rep Med

Venetoclax acts as an immunometabolic modulator to potentiate adoptive NK cell immunotherapy against leukemia. [Abstract]

2024 Jun 18;5(6):101580. PMID: 38776913

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (113.32 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1332 mL

5.6662 mL

11.3325 mL

5 mM

0.2266 mL

1.1332 mL

2.2665 mL

10 mM

0.1133 mL

0.5666 mL

1.1332 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: 2.5 mg/mL (2.83 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (292 KB)
SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Ailawadhi S, et al. Novel BCL-2 Inhibitor Lisaftoclax in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematologic Malignancies: First-in-Human Open-Label Trial. Clinical cancer research : an official journal of the American Association for Cancer Research. 2023 Jul 05;29(13):2385-2393. [Content Brief]

[2]. Deng J, et al. Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy. Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Dec 15;28(24):5455-5468. [Content Brief]

[3]. Davids MS, et al. Lisaftoclax (APG-2575) demonstrates activity and safety when given with accelerated ramp-up and then combined with acalabrutinib or rituximab in patients (pts) with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including those with prior exposure to venetoclax. Blood. 2024;144(Suppl 1):4614.

[4]. Ailawadhi S, et al. Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (pts) with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light-Chain (AL) Amyloidosis. Blood. 2024;144(Suppl 1):1022.

[5]. Wang CW, Chen J. N-(phenylsulfonyl)benzamides and related compounds as bcl-2 inhibitors. WO2018027097 A1. 2018 Feb 8.

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.1332 mL	5.6662 mL	11.3325 mL	28.3312 mL
	5 mM	0.2266 mL	1.1332 mL	2.2665 mL	5.6662 mL
	10 mM	0.1133 mL	0.5666 mL	1.1332 mL	2.8331 mL
	15 mM	0.0755 mL	0.3777 mL	0.7555 mL	1.8887 mL
	20 mM	0.0567 mL	0.2833 mL	0.5666 mL	1.4166 mL
	25 mM	0.0453 mL	0.2266 mL	0.4533 mL	1.1332 mL
	30 mM	0.0378 mL	0.1889 mL	0.3777 mL	0.9444 mL
	40 mM	0.0283 mL	0.1417 mL	0.2833 mL	0.7083 mL
	50 mM	0.0227 mL	0.1133 mL	0.2266 mL	0.5666 mL
	60 mM	0.0189 mL	0.0944 mL	0.1889 mL	0.4722 mL
	80 mM	0.0142 mL	0.0708 mL	0.1417 mL	0.3541 mL
	100 mM	0.0113 mL	0.0567 mL	0.1133 mL	0.2833 mL

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

Product Name:
CAS No.:
Species:
Purity:
Quantity:

Lisaftoclax

Publications Citing Use of MedChemExpress (MCE) Lisaftoclax

All Bcl-2 Family Isoforms