Synonym
ML216; ML-216; ML 216; CID-4985229; CID 4985229; CID4985229.
IUPAC/Chemical Name
1-(4-fluoro-3-(trifluoromethyl)phenyl)-3-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)urea
InChi Key
WMCOYUSJXXCHFH-UHFFFAOYSA-N
InChi Code
InChI=1S/C15H9F4N5OS/c16-11-2-1-9(7-10(11)15(17,18)19)21-13(25)22-14-24-23-12(26-14)8-3-5-20-6-4-8/h1-7H,(H2,21,22,24,25)
SMILES Code
O=C(NC1=NN=C(C2=CC=NC=C2)S1)NC3=CC=C(F)C(C(F)(F)F)=C3
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
BLM helicase is a DNA unwinding enzyme critical in DNA repair via the homologous recombination (HR) pathway. Mutations of the BLM gene result in diminished BLM helicase activity and can cause Bloom’s Syndrome, which is characterized by a long list of phenotypes, including predisposition to cancers. Similar to other DNA repair enzymes, inhibition of BLM helicase results in sensitization of tumor cells to conventional cancer therapies, such as camptothecin. Currently, there are no known small molecule inhibitors of BLM helicase; thus, the discovery of a novel small molecule inhibitor would help define the mechanism of action of the enzyme and provide a basis for future development of inhibitors and cancer therapeutics.
Biological target:
ML216 (CID-49852229) is a potent, selective and cell permeable inhibitor of the DNA unwinding activity of BLM helicase with IC50s of 2.98 μM and 0.97 μM for BLM and BLM, respectively.
In vitro activity:
Using this isogenic pair of cells, it was sought to identify whether ML216 could influence cell growth and SCE induction in a BLM (Bloom’s syndrome protein)-specific manner. It was found that ML216 was an inhibitor of the proliferation of PSNF5 cells, but not of PSNG13 cells, and did so in a concentration-dependent manner. Moreover, ML216 treatment led to a statistically significant increase in the frequency of sister chromatid exchanges (SCEs) in PSNF5 cells, but not in PSNG13 cells. In each experiment conducted thus far, the exposure time of cells to ML216 was 24–72 hours. It was then asked whether ML216 could induce SCEs in PSNF5 cells if present only during the last 8 hours of the experiment prior to collection of cells in metaphase. That way, BLM would be targeted by ML216 only during the second S-phase of exposure to BrdU, because SCE analysis requires that BrdU be present during two consecutive S-phases before cells are arrested with colcemid and metaphases are harvested. It was found that this shorter exposure led to a statistically significant increase in the frequency of SCEs in PSNF5 cells expressing BLM.
Reference: Chem Biol. 2013 Jan 24;20(1):55-62. https://pubmed.ncbi.nlm.nih.gov/23352139/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
29.0 |
75.65 |
|
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
383.32
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. Suthram N, Padhi S, Jha P, Bhattacharyya S, Bulusu G, Roy A, Bhattacharyya MK. Elucidation of DNA Repair Function of PfBlm and Potentiation of Artemisinin Action by a Small-Molecule Inhibitor of RecQ Helicase. mSphere. 2020 Nov 25;5(6):e00956-20. doi: 10.1128/mSphere.00956-20. PMID: 33239368; PMCID: PMC7690958.
2. Nguyen GH, Dexheimer TS, Rosenthal AS, Chu WK, Singh DK, Mosedale G, Bachrati CZ, Schultz L, Sakurai M, Savitsky P, Abu M, McHugh PJ, Bohr VA, Harris CC, Jadhav A, Gileadi O, Maloney DJ, Simeonov A, Hickson ID. A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells. Chem Biol. 2013 Jan 24;20(1):55-62. doi: 10.1016/j.chembiol.2012.10.016. PMID: 23352139; PMCID: PMC3558928.
In vitro protocol:
1. Suthram N, Padhi S, Jha P, Bhattacharyya S, Bulusu G, Roy A, Bhattacharyya MK. Elucidation of DNA Repair Function of PfBlm and Potentiation of Artemisinin Action by a Small-Molecule Inhibitor of RecQ Helicase. mSphere. 2020 Nov 25;5(6):e00956-20. doi: 10.1128/mSphere.00956-20. PMID: 33239368; PMCID: PMC7690958.
2. Nguyen GH, Dexheimer TS, Rosenthal AS, Chu WK, Singh DK, Mosedale G, Bachrati CZ, Schultz L, Sakurai M, Savitsky P, Abu M, McHugh PJ, Bohr VA, Harris CC, Jadhav A, Gileadi O, Maloney DJ, Simeonov A, Hickson ID. A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells. Chem Biol. 2013 Jan 24;20(1):55-62. doi: 10.1016/j.chembiol.2012.10.016. PMID: 23352139; PMCID: PMC3558928.
1: Hashitani H, Mitsui R, Masaki S, Van Helden DF. Pacemaker role of pericytes in
generating synchronized spontaneous Ca2+ transients in the myenteric
microvasculature of the guinea-pig gastric antrum. Cell Calcium. 2015
Nov;58(5):442-56. doi: 10.1016/j.ceca.2015.06.012. Epub 2015 Jun 30. PubMed PMID:
26153078.
2: Rosenthal AS, Dexheimer TS, Nguyen G, Gileadi O, Vindigni A, Simeonov A,
Jadhav A, Hickson I, Maloney DJ. Discovery of ML216, a Small Molecule Inhibitor
of Bloom (BLM) Helicase. 2011 Apr 15 [updated 2013 Feb 28]. 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/NBK154497/
PubMed PMID: 24027802.
3: Rosenthal AS, Dexheimer TS, Gileadi O, Nguyen GH, Chu WK, Hickson ID, Jadhav
A, Simeonov A, Maloney DJ. Synthesis and SAR studies of
5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of
Bloom helicase. Bioorg Med Chem Lett. 2013 Oct 15;23(20):5660-6. doi:
10.1016/j.bmcl.2013.08.025. Epub 2013 Aug 13. PubMed PMID: 24012121; PubMed
Central PMCID: PMC3824626.
4: Nguyen GH, Dexheimer TS, Rosenthal AS, Chu WK, Singh DK, Mosedale G, Bachrati
CZ, Schultz L, Sakurai M, Savitsky P, Abu M, McHugh PJ, Bohr VA, Harris CC,
Jadhav A, Gileadi O, Maloney DJ, Simeonov A, Hickson ID. A small molecule
inhibitor of the BLM helicase modulates chromosome stability in human cells. Chem
Biol. 2013 Jan 24;20(1):55-62. doi: 10.1016/j.chembiol.2012.10.016. PubMed PMID:
23352139; PubMed Central PMCID: PMC3558928.
