ML-323
featured

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

MedKoo CAT#: 406534

CAS#: 1572414-83-5

Description: ML323 is a selective and highly potent USP1-UAF1 inhibitor links deubiquitination to DNA damage responses. ML323 inhibits the USP1-UAF1 deubiquitinase complex with excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases. ML323 potentiates cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells. USP1-UAF1 is a key regulator of the DNA damage response and a target for overcoming resistance to the platinum-based anticancer drugs.


Chemical Structure

img
ML-323
CAS# 1572414-83-5

Theoretical Analysis

MedKoo Cat#: 406534
Name: ML-323
CAS#: 1572414-83-5
Chemical Formula: C23H24N6
Exact Mass: 384.20624
Molecular Weight: 384.48
Elemental Analysis: C, 71.85; H, 6.29; N, 21.86

Price and Availability

Size Price Availability Quantity
25.0mg USD 90.0 Same day
50.0mg USD 150.0 Same day
100.0mg USD 250.0 Same day
200.0mg USD 450.0 Same day
500.0mg USD 950.0 Same day
1.0g USD 1750.0 2 Weeks
2.0g USD 3250.0 2 Weeks
Bulk inquiry

Synonym: ML323; ML 323; ML-323.

IUPAC/Chemical Name: N-(4-(1H-1,2,3-triazol-1-yl)benzyl)-2-(2-isopropylphenyl)-5-methylpyrimidin-4-amine

InChi Key: VUIRVWPJNKZOSS-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H24N6/c1-16(2)20-6-4-5-7-21(20)23-24-14-17(3)22(27-23)25-15-18-8-10-19(11-9-18)29-13-12-26-28-29/h4-14,16H,15H2,1-3H3,(H,24,25,27)

SMILES Code: CC1=CN=C(C2=CC=CC=C2C(C)C)N=C1NCC3=CC=C(N4N=NC=C4)C=C3

Appearance: white 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: ML-323 is a reversible, potent USP1-UAF1 inhibitor with IC50 of 76 nM in a Ub-Rho assay.
In vitro activity: Analysis of cells by immunofluorescence method and confocal microscopy showed that the ML323 inhibitor affects the localization of the USP1 protein (Fig. 3). Despite that USP1 protein is a nuclear protein, after 1.5 h incubation with ML323, this study found not only nuclear but also cytoplasmic localization in some cells. By the third hour of incubation with ML323 protein USP1 was detected mainly in the cytoplasm, and in some cells, the protein was not detected at all. In this case, the РCC decreased from 0.63 to 0.23 as compared to the control. The MOC indices also decreased, both MOC M1 (fraction of USP1 overlapping Bcr-Abl) and MOC M2 indicating the almost complete absence of overlap of localization signals of Bсr-Abl oncoprotein with USP1 protein. After 24 h of incubation with ML323 only cytoplasmic localization of USP1 protein remains. Thus, the action of the ML323 inhibitor alters the localization of USP1 protein and significantly reduces the level of colocalization with Bcr-Abl oncoprotein. Reference: Exp Oncol. 2020 Jun;42(2):109-114. https://pubmed.ncbi.nlm.nih.gov/32602291/
In vivo activity: ML323 treatment inhibited VSV-induced IFN-β production in peritoneal lavage (Fig. 5 I) and suppressed TBK1 protein expression in peritoneal exudate cells (Fig. 5 J). Furthermore, VSV infection induced IFN-β secretion was much less in sera of ML323-treated mice than in that of control mice (Fig. 5 K). Accordingly, IFN-β mRNA expression in the liver, lung, and spleen of ML323-treated mice was lower than that in controls (Fig. 5 L). In accordance with reduced IFN-β expression, VSV replication in the liver, lung, and spleen of ML323-treated mice was higher than that in controls (Fig. 5 M). Severe infiltration of immune cells was observed in the lungs of ML323-treated mice, compared with that of control mice after VSV infection (Fig. 5 N). Reference: J Exp Med. 2017 Dec 4; 214(12): 3553–3563. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716033/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 44.61 116.03
DMF 20.0 52.02
Ethanol 32.15 83.62
Ethanol:PBS (pH 7.2) (1:6) 0.14 0.36

Preparing Stock Solutions

The following data is based on the product molecular weight 384.48 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. Antonenko SV, Telegeev GD. Inhibition of USP1, a new partner of Bcr-Abl, results in decrease of Bcr-Abl level in K562 cells. Exp Oncol. 2020 Jun;42(2):109-114. doi: 10.32471/exp-oncology.2312-8852.vol-42-no-2.14533. PMID: 32602291. 2. Kim JY, Choung PH. USP1 inhibitor ML323 enhances osteogenic potential of human dental pulp stem cells. Biochem Biophys Res Commun. 2020 Sep 17;530(2):418-424. doi: 10.1016/j.bbrc.2020.05.095. Epub 2020 Jun 14. PMID: 32546349. 3. Yu Z, Song H, Jia M, Zhang J, Wang W, Li Q, Zhang L, Zhao W. USP1-UAF1 deubiquitinase complex stabilizes TBK1 and enhances antiviral responses. J Exp Med. 2017 Dec 4;214(12):3553-3563. doi: 10.1084/jem.20170180. Epub 2017 Nov 14. PMID: 29138248; PMCID: PMC5716033.
In vitro protocol: 1. Antonenko SV, Telegeev GD. Inhibition of USP1, a new partner of Bcr-Abl, results in decrease of Bcr-Abl level in K562 cells. Exp Oncol. 2020 Jun;42(2):109-114. doi: 10.32471/exp-oncology.2312-8852.vol-42-no-2.14533. PMID: 32602291. 2. Kim JY, Choung PH. USP1 inhibitor ML323 enhances osteogenic potential of human dental pulp stem cells. Biochem Biophys Res Commun. 2020 Sep 17;530(2):418-424. doi: 10.1016/j.bbrc.2020.05.095. Epub 2020 Jun 14. PMID: 32546349.
In vivo protocol: 1. Yu Z, Song H, Jia M, Zhang J, Wang W, Li Q, Zhang L, Zhao W. USP1-UAF1 deubiquitinase complex stabilizes TBK1 and enhances antiviral responses. J Exp Med. 2017 Dec 4;214(12):3553-3563. doi: 10.1084/jem.20170180. Epub 2017 Nov 14. PMID: 29138248; PMCID: PMC5716033.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Liang Q, Dexheimer TS, Zhang P, Rosenthal AS, Villamil MA, You C, Zhang Q, Chen J, Ott CA, Sun H, Luci DK, Yuan B, Simeonov A, Jadhav A, Xiao H, Wang Y, Maloney DJ, Zhuang Z. A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses. Nat Chem Biol. 2014 Apr;10(4):298-304. doi: 10.1038/nchembio.1455. Epub 2014 Feb 16. PubMed PMID: 24531842.

ML-323

25.0mg / USD 90.0


Additional Information