A-1210477
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MedKoo CAT#: 407156

CAS#: 1668553-26-1

Description: A-1210477 is a potent and selective MCL-1 inhibitor. A-1210477 induces the hallmarks of intrinsic apoptosis and demonstrates single agent killing of multiple myeloma and non-small cell lung cancer cell lines. A-1210477 synergizes with the BCL-2/BCL-XL inhibitor navitoclax to kill a variety of cancer cell lines. A-1210477 is a potential therapeutics for the treatment of cancer. The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target.


Chemical Structure

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A-1210477
CAS# 1668553-26-1

Theoretical Analysis

MedKoo Cat#: 407156
Name: A-1210477
CAS#: 1668553-26-1
Chemical Formula: C46H55N7O7S
Exact Mass: 849.38837
Molecular Weight: 850.05
Elemental Analysis: C, 65.00; H, 6.52; N, 11.53; O, 13.17; S, 3.77

Price and Availability

Size Price Availability Quantity
10.0mg USD 120.0 Same Day
25.0mg USD 250.0 Same Day
50.0mg USD 450.0 Same Day
100.0mg USD 750.0 Same Day
200.0mg USD 1350.0 Same Day
500.0mg USD 2650.0 Same Day
1.0g USD 3850.0 2 Weeks
2.0g USD 6450.0 2 Weeks
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Synonym: A-1210477; A 1210477; A1210477.

IUPAC/Chemical Name: 7-(5-((4-(4-(N,N-dimethylsulfamoyl)piperazin-1-yl)phenoxy)methyl)-1,3-dimethyl-1H-pyrazol-4-yl)-1-(2-morpholinoethyl)-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylic acid

InChi Key: XMVAWGSQPHFXKU-UHFFFAOYSA-N

InChi Code: InChI=1S/C46H55N7O7S/c1-33-43(41(49(4)47-33)32-60-36-19-17-35(18-20-36)51-22-24-52(25-23-51)61(56,57)48(2)3)40-14-8-13-38-39(15-9-29-59-42-16-7-11-34-10-5-6-12-37(34)42)45(46(54)55)53(44(38)40)26-21-50-27-30-58-31-28-50/h5-8,10-14,16-20H,9,15,21-32H2,1-4H3,(H,54,55)

SMILES Code: O=C(C(N1CCN2CCOCC2)=C(CCCOC3=C(C=CC=C4)C4=CC=C3)C5=C1C(C6=C(COC7=CC=C(N8CCN(S(=O)(N(C)C)=O)CC8)C=C7)N(C)N=C6C)=CC=C5)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: >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: A-1210477 is a MCL-1 inhibitor with an IC50 of 26.2 nM.
In vitro activity: Esophageal cell proliferation was reduced markedly following A-1210477 treatment. The apoptotic cells of these ESCC (esophageal squamous cell carcinoma) were evaluated after A-1210477 treatment by detecting cleaved caspase3 expression with quantitative IHC (immunohistochemistry). There was a statistically significant increase in labeling indices when control ESCC (1.2 ± 0.8) was compared with low dose (8.0 ± 3.1) and high dose ones (14.0 ± 4.5) (Figure 4A–4D). The percentage of TUNEL positive cells increased dose dependently from 1.9 % in DMSO mice to 8.9 % (p < 0.05) in low-dose A-1210477 mice and 19.0 % (p < 0.05) in high-dose A-1210477 mice (Figure 4E–4N). These data clearly demonstrated A-1210477 treatment led to increased cell death in mouse ESCC. Reference: Oncotarget. 2017 Jun 28;8(70):114457-114462. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777705/
In vivo activity: To test whether MCL-1 plays a role in ESCC cancer progression, mice at 20 weeks after initial 4NQO exposure were injected with control vehicle, lose dose and high dose of A-1210477 daily for 4 weeks. A-1210477-treated mice had developed fewer tumors than the vehicle-treated mice did in a dose dependent manner (Figure 2A). Similarly, there was significant less body weight loss in the A-1210477-treatment group mice compared with the control ones (Figure 2B). Microscopically, there was also less malignancy formation in the esophagus following A-1210477-treatment (Figure 2C–2E). Reference: Oncotarget. 2017 Jun 28;8(70):114457-114462. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777705/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 5.9 6.94

Preparing Stock Solutions

The following data is based on the product molecular weight 850.05 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. Lin J, Fu D, Dai Y, Lin J, Xu T. Mcl-1 inhibitor suppresses tumor growth of esophageal squamous cell carcinoma in a mouse model. Oncotarget. 2017 Jun 28;8(70):114457-114462. doi: 10.18632/oncotarget.18772. PMID: 29383093; PMCID: PMC5777705.
In vitro protocol: 1. Lin J, Fu D, Dai Y, Lin J, Xu T. Mcl-1 inhibitor suppresses tumor growth of esophageal squamous cell carcinoma in a mouse model. Oncotarget. 2017 Jun 28;8(70):114457-114462. doi: 10.18632/oncotarget.18772. PMID: 29383093; PMCID: PMC5777705.
In vivo protocol: 1. Lin J, Fu D, Dai Y, Lin J, Xu T. Mcl-1 inhibitor suppresses tumor growth of esophageal squamous cell carcinoma in a mouse model. Oncotarget. 2017 Jun 28;8(70):114457-114462. doi: 10.18632/oncotarget.18772. PMID: 29383093; PMCID: PMC5777705.

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1: Xiao Y, Nimmer P, Sheppard GS, Bruncko M, Hessler P, Lu X, Roberts-Rapp L,
Pappano WN, Elmore SW, Souers AJ, Leverson JD, Phillips DC. MCL-1 Is a Key
Determinant of Breast Cancer Cell Survival: Validation of MCL-1 Dependency
Utilizing a Highly Selective Small Molecule Inhibitor. Mol Cancer Ther. 2015
Aug;14(8):1837-47. doi: 10.1158/1535-7163.MCT-14-0928. Epub 2015 May 26. PubMed
PMID: 26013319.

2: Leverson JD, Zhang H, Chen J, Tahir SK, Phillips DC, Xue J, Nimmer P, Jin S,
Smith M, Xiao Y, Kovar P, Tanaka A, Bruncko M, Sheppard GS, Wang L, Gierke S,
Kategaya L, Anderson DJ, Wong C, Eastham-Anderson J, Ludlam MJ, Sampath D,
Fairbrother WJ, Wertz I, Rosenberg SH, Tse C, Elmore SW, Souers AJ. Potent and
selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell
killing activity as single agents and in combination with ABT-263 (navitoclax).
Cell Death Dis. 2015 Jan 15;6:e1590. doi: 10.1038/cddis.2014.561. PubMed PMID:
25590800.