Synonym
ML241; ML-241; ML 241; ML241 HCl; ML241 hydrochloride
IUPAC/Chemical Name
2-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine hydrochloride
InChi Key
DYHMHNNBOLCULH-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H24N4O.ClH/c1-2-8-17(9-3-1)16-24-22-18-10-4-5-11-19(18)25-23(26-22)27-14-15-28-21-13-7-6-12-20(21)27;/h1-3,6-9,12-13H,4-5,10-11,14-16H2,(H,24,25,26);1H
SMILES Code
[H]Cl.C1(N2C3=CC=CC=C3OCC2)=NC(NCC4=CC=CC=C4)=C5CCCCC5=N1
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
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:
ML241 hydrochloride is a potent p97 inhibitor, inhibiting p97 ATPase with IC50 value of 100 nM.
In vitro activity:
Consistent with the role of p97 in the ubiquitin–proteasome system (UPS), ML240 and ML241, like the parent compound DBeQ, caused accumulation of ubiquitin conjugates in the nuclear plus membrane and cytosolic compartments at concentrations of 5–10 μm (Figure 4a). Interestingly, ML241 caused stronger accumulation than ML240, even though ML240 was more potent at stabilizing UbG76V–GFP. This, along with the cell proliferation data, points to unexpected complexity in the mechanism of action of these compounds.
Reference: ChemMedChem. 2013 Feb; 8(2): 297–312. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662613/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
54.0 |
132.05 |
|
| Ethanol |
20.0 |
48.91 |
|
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
408.93
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, 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.
2. Fang CJ, Gui L, Zhang X, Moen DR, Li K, Frankowski KJ, Lin HJ, Schoenen FJ, Chou TF. Evaluating p97 inhibitor analogues for their domain selectivity and potency against the p97-p47 complex. ChemMedChem. 2015 Jan;10(1):52-6. doi: 10.1002/cmdc.201402420. Epub 2014 Nov 6. PMID: 25377500; PMCID: PMC4280364.
In vitro protocol:
1. 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.
2. Fang CJ, Gui L, Zhang X, Moen DR, Li K, Frankowski KJ, Lin HJ, Schoenen FJ, Chou TF. Evaluating p97 inhibitor analogues for their domain selectivity and potency against the p97-p47 complex. ChemMedChem. 2015 Jan;10(1):52-6. doi: 10.1002/cmdc.201402420. Epub 2014 Nov 6. PMID: 25377500; PMCID: PMC4280364.
1: Fang CJ, Gui L, Zhang X, Moen DR, Li K, Frankowski KJ, Lin HJ, Schoenen FJ, Chou TF. Evaluating p97 Inhibitor Analogues for Their Domain Selectivity and Potency against the p97-p47 Complex. ChemMedChem. 2015 Jan;10(1):52-6. doi: 10.1002/cmdc.201402420. Epub 2014 Nov 6. PubMed PMID: 25377500; PubMed Central PMCID: PMC4280364.
2: 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. PubMed PMID: 24878061; PubMed Central PMCID: PMC4102644.
3: Chou TF, Li K, Nordin BE, Porubsky P, Frankowski K, Patricelli MP, Aubé J, Schoenen FJ, Deshaies R. Selective, reversible inhibitors of the AAA ATPase p97. 2011 Apr 14 [updated 2013 May 01]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK133422/ PubMed PMID: 23658965.
4: 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. PubMed PMID: 23316025; PubMed Central PMCID: PMC3662613.
