ML240 | CAS#1346527-98-7 | p97 ATPase inhibitor

MedKoo Cat#: 407241 | Name: ML240

Description:

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

ML240 is a ATP-competitive inhibitor of p97 ATPase (IC50 = 110 nM). p97 is a homohexamer with each protomer containing a protein−protein interaction domain at the N-terminus, a D1 ATPase/hexamerization domain, and the catalytic D2 ATPase domain. p97 inhibitors could have improved therapeutic potential in tumor types currently treated by proteasome inhibitors.

Chemical Structure

ML240

CAS#1346527-98-7

Theoretical Analysis

MedKoo Cat#: 407241

Name: ML240

CAS#: 1346527-98-7

Chemical Formula: C23H20N6O

Exact Mass: 396.1699

Molecular Weight: 396.45

Elemental Analysis: C, 69.68; H, 5.09; N, 21.20; O, 4.04

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
200mg	USD 950.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
500mg	USD 1,850.00	Ready to ship
1g	USD 4,250.00	2 Weeks
2g	USD 5,450.00	2 Weeks
5g	USD 7,850.00	2 Weeks

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Related CAS #

No Data

Synonym

ML240; ML-240; ML 240.

IUPAC/Chemical Name

2-(2-Amino-1H-benzimidazole-1-yl)-8-methoxy-N-(phenylmethyl)-4-quinazolinamine

InChi Key

NHAMBLRUUJAFOY-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H20N6O/c1-30-19-13-7-10-16-20(19)27-23(28-21(16)25-14-15-8-3-2-4-9-15)29-18-12-6-5-11-17(18)26-22(29)24/h2-13H,14H2,1H3,(H2,24,26)(H,25,27,28)

SMILES Code

COC1=CC=CC2=C(NCC3=CC=CC=C3)N=C(N4C5=CC=CC=C5N=C4N)N=C12

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T07K25

QC Data

View QC data: current batch, Lot#A8T07K25

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ML240 is a potent p97 inhibitor, inhibiting p97 ATPase with IC50 value of 100 nM.

In vitro activity:

Three potent, ATP-competitive p97 inhibitors (DBeQ, ML240, and ML241; Fig. 4A) were identified. To investigate whether these four p97 compounds inhibit the ATPase activity of D1, D2, or both domains, IC50 values were determined for WT p97 and five variants in the presence of 200 µM or 875 µM ATP. Lower potencies were observed for inhibition of WT p97 (roughly 2 to 5-fold increases in IC50; Fig. 4 and Tables S4 and S5). There was a 2.7- to 10-fold increase in IC50 ML240, and ML241 (Figs. 4 B–D). These increases in IC50 can be partly explained by the 2.4-fold decrease in Km for D1-E305Q, because ATP competitive inhibitors are sensitive to the levels of ATP binding (Fig. 3E). In contrast to the smaller effects found for the D1 D1-E305Q mutant, ML240 was inactive toward D2 mutants D2-E578Q and D2-K524A, and toward ND1L. Thus, both ML240 and ML241 were D2 selective inhibitors (Figs. 4 C and D). D1 D1-K251A mutation increased the IC50 for ML240 by 27-fold with 200 µM ATP and ML240 can not inhibit D1 D1-K251A with 875 µM ATP, suggesting that the architecture of the D2 active site was changed significantly due to the mutation and/or due to the absence of nucleotide binding to D1. In summary, ML240 is elective against the D2 domain. Reference: J Mol Biol. 2014 Jul 29; 426(15): 2886–2899. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102644/

In vivo activity:

TBD

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	7.0	17.66

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 396.45 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. Chou TF, Bulfer SL, Weihl CC, Li K, Lis LG, Walters MA, Schoenen FJ, Lin HJ, Deshaies RJ, Arkin MR. Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains. J Mol Biol. 2014 Jul 29;426(15):2886-99. doi: 10.1016/j.jmb.2014.05.022. Epub 2014 May 27. PMID: 24878061; PMCID: PMC4102644. 2. Chou TF, Li K, Frankowski KJ, Schoenen FJ, Deshaies RJ. Structure-activity relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase. ChemMedChem. 2013 Feb;8(2):297-312. doi: 10.1002/cmdc.201200520. Epub 2013 Jan 11. PMID: 23316025; PMCID: PMC3662613.

In vitro protocol:

In vivo protocol:

TBD