Synonym
PF-9366; PF 9366; PF9366
IUPAC/Chemical Name
2-(7-Chloro-5-phenyl-[1,2,4]triazolo[4,3-a]quinolin-1-yl)-N,N-dimethylethan-1-amine
InChi Key
LYLASWLQCMKZAT-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H19ClN4/c1-24(2)11-10-19-22-23-20-13-16(14-6-4-3-5-7-14)17-12-15(21)8-9-18(17)25(19)20/h3-9,12-13H,10-11H2,1-2H3
SMILES Code
CN(C)CCC1=NN=C2N1C3=C(C=C(Cl)C=C3)C(C4=CC=CC=C4)=C2
Purity
>96% (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:
PF-9366 is a human methionine adenosyltransferase 2A (Mat2A) inhibitor, with an IC50 of 420 nM and a Kd of 170 nM.
In vitro activity:
Untreated (DMSO control) CRISPR/Cas9-MLLr cells presented an immature morphology whereas treatment with PF-9366 resulted in macrophage-like cells with an increase of apoptotic cells consistent with the upregulation of CD14 expression (Figure 4A,B). Consistently, a trend to downregulate the target gene expression of MEIS1 and HOXA9 upon PF-9366 treatment was observed, irrespective of day 4 or 6, although significance was not reached in all performed experiments (Figure 4C). These data suggest that the inhibition of MAT2A results in cell differentiation, induction of cell cycle arrest, and finally apoptosis in MLL fusion protein-driven leukemogenesis without any impact on control cells.
Reference: Cancers (Basel). 2020 May; 12(5): 1342. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281730/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
2.0 |
5.70 |
|
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
350.85
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. Secker KA, Bloechl B, Keppeler H, Duerr-Stoerzer S, Schmid H, Schneidawind D, Jeong J, Hentrich T, Schulze-Hentrich JM, Schneidawind C. MAT2A as Key Regulator and Therapeutic Target in MLLr Leukemogenesis. Cancers (Basel). 2020 May 24;12(5):1342. doi: 10.3390/cancers12051342. PMID: 32456310; PMCID: PMC7281730.
2. Quinlan CL, Kaiser SE, Bolaños B, Nowlin D, Grantner R, Karlicek-Bryant S, Feng JL, Jenkinson S, Freeman-Cook K, Dann SG, Wang X, Wells PA, Fantin VR, Stewart AE, Grant SK. Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A. Nat Chem Biol. 2017 Jul;13(7):785-792. doi: 10.1038/nchembio.2384. Epub 2017 May 29. PMID: 28553945.
In vitro protocol:
1. Secker KA, Bloechl B, Keppeler H, Duerr-Stoerzer S, Schmid H, Schneidawind D, Jeong J, Hentrich T, Schulze-Hentrich JM, Schneidawind C. MAT2A as Key Regulator and Therapeutic Target in MLLr Leukemogenesis. Cancers (Basel). 2020 May 24;12(5):1342. doi: 10.3390/cancers12051342. PMID: 32456310; PMCID: PMC7281730.
2. Quinlan CL, Kaiser SE, Bolaños B, Nowlin D, Grantner R, Karlicek-Bryant S, Feng JL, Jenkinson S, Freeman-Cook K, Dann SG, Wang X, Wells PA, Fantin VR, Stewart AE, Grant SK. Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A. Nat Chem Biol. 2017 Jul;13(7):785-792. doi: 10.1038/nchembio.2384. Epub 2017 May 29. PMID: 28553945.
1: Quinlan CL, Kaiser SE, Bolaños B, Nowlin D, Grantner R, Karlicek-Bryant S, Feng JL, Jenkinson S, Freeman-Cook K, Dann SG, Wang X, Wells PA, Fantin VR, Stewart AE, Grant SK. Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A. Nat Chem Biol. 2017 May 29. doi: 10.1038/nchembio.2384. [Epub ahead of print] PubMed PMID: 28553945.
Secker KA, Bloechl B, Keppeler H, Duerr-Stoerzer S, Schmid H, Schneidawind D, Jeong J, Hentrich T, Schulze-Hentrich JM, Schneidawind C. MAT2A as Key Regulator and Therapeutic Target in MLLr Leukemogenesis. Cancers (Basel). 2020 May 24;12(5):1342. doi: 10.3390/cancers12051342. PMID: 32456310; PMCID: PMC7281730.
Acosta CH, Clemons GA, Citadin CT, Carr WC, Udo MSB, Tesic V, Sanicola HW, Freelin AH, Toms JB, Jordan JD, Guthikonda B, Wu CY, Lee RH, Lin HW. A role for protein arginine methyltransferase 7 in repetitive and mild traumatic brain injury. Neurochem Int. 2023 Jun;166:105524. doi: 10.1016/j.neuint.2023.105524. Epub 2023 Apr 6. PMID: 37030326; PMCID: PMC10988608.
