AMG-176

Alias: tapotoclaxum; tapotoclax; AMG-176; AMG176; AMG 176

Cat No.:V3448 Purity: ≥98%

COA Product Data Instructions for use SDS

AMG-176 (AMG176; tapotoclax) is a novel, potent, selective and orally bioavailable inhibitor of MCL-1 (myeloid cell leukemia-1) with aKiof 0.13 nM.

AMG-176 Chemical Structure CAS No.: 1883727-34-1
Product category: Bcl-2

This product is for research use only, not for human use. We do not sell to patients.

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2mg
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10mg
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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

AMG-176 (AMG176; tapotoclax) is a novel, potent, selective and orally bioavailable inhibitor of MCL-1 (myeloid cell leukemia-1) with a Ki of 0.13 nM. Potential pro-apoptotic and anti-cancer effects of AMG-176 exist. MCL-1 is bound by AMG 176, which then stops it from working. This causes apoptosis in tumor cells and interferes with the formation of MCL-1/Bcl-2-like protein 11 (BCL2L11; BIM) complexes. The Bcl-2 family of proteins member MCL-1, an anti-apoptotic protein, is upregulated in cancer cells and supports the survival of tumor cells.

Biological Activity I Assay Protocols (From Reference)

Targets	Mcl-1 (Ki = 0.13 nM)
ln Vitro	Tapoclax is a compound that has the ability to stimulate cell color development and anti-tumor action. It also promotes the production of MCL-1 (Ki=0.13 nM) in inducible myeloid leukemia cells. After then, tapotoclax attaches to MCL-1 and prevents its function. It stimulates tumor cells and interferes with the formation of the MCL-1/Bcl-2-like protein 11 (BCL2L11; BIM) complex [1][2].
References	[1]. Caenepeel S, et al. AMG 176, a Selective MCL1 Inhibitor, is Effective in Hematological Cancer Models Alone and in Combination with Established Therapies. Cancer Discov. 2018 Sep 25. pii: CD-18-0387. [2]. Garner TP, et al. Progress in targeting the BCL-2 family of proteins. Curr Opin Chem Biol. 2017 Aug;39:133-142.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C33H41CLN2O5S
Molecular Weight	613.207047224045
Exact Mass	612.24
Elemental Analysis	C, 64.64; H, 6.74; Cl, 5.78; N, 4.57; O, 13.05; S, 5.23
CAS #	1883727-34-1
Related CAS #	1883727-34-1
Appearance	Solid powder
SMILES	C[C@H]1C/C=C/[C@@H]([C@@H]2CC[C@H]2CN3C[C@@]4(CCCC5=C4C=CC(=C5)Cl)COC6=C3C=C(C=C6)C(=O)NS(=O)(=O)[C@@H]1C)OC
InChi Key	JQNINBDKGLWYMU-GEAQBIRJSA-N
InChi Code	InChI=1S/C33H41ClN2O5S/c1-21-6-4-8-30(40-3)27-12-9-25(27)18-36-19-33(15-5-7-23-16-26(34)11-13-28(23)33)20-41-31-14-10-24(17-29(31)36)32(37)35-42(38,39)22(21)2/h4,8,10-11,13-14,16-17,21-22,25,27,30H,5-7,9,12,15,18-20H2,1-3H3,(H,35,37)/b8-4+/t21-,22+,25-,27+,30-,33-/m0/s1
Chemical Name	(3'R,4S,6'R,7'S,8'E,11'S,12'R)-7-chloro-7'-methoxy-11',12'-dimethyl-13',13'-dioxospiro[2,3-dihydro-1H-naphthalene-4,22'-20-oxa-13lambda6-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16(25),17,19(24)-tetraene]-15'-one
Synonyms	tapotoclaxum; tapotoclax; AMG-176; AMG176; AMG 176
HS Tariff Code	2934.99.9001
Storage	Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)	DMSO: ~62.5 mg/mL (~101.9 mM)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6308 mL	8.1538 mL	16.3076 mL
	5 mM	0.3262 mL	1.6308 mL	3.2615 mL
	10 mM	0.1631 mL	0.8154 mL	1.6308 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05209152	Recruiting	Drug: AMG 176 Drug: Azacitidine	Higher Risk Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia	Amgen	September 1, 2019	Phase 1
NCT02675452	Recruiting	Drug: AMG 176 Drug: Azacitidine	Relapsed or Refractory Multiple Myeloma Relapsed or Refractory Acute Myeloid Leukemia	Amgen	June 13, 2016	Phase 1
NCT03797261	Terminated	Drug: Venetoclax Drug: AMG 176	Acute Myeloid Leukemia Non-Hodgkin's Lymphoma	AbbVie	March 18, 2019	Phase 1

Biological Data

Optimization of chemical matter to AMG 176. Cancer Discov . 2018 Dec;8(12):1582-1597.
AMG 176 exhibits robust single-agent activity in vivo. Cancer Discov . 2018 Dec;8(12):1582-1597.
AMG 176 exhibits activity when combined with clinically relevant agents that target hematologic malignancies. Cancer Discov . 2018 Dec;8(12):1582-1597.