SHMT-IN-1 (compound (±)-46) is a potent inhibitor of plasma serine hydroxymethyltransferase (SHMT). SHMT-IN-1 has anti-tumor effects.

Physicochemical Properties

Molecular Formula	C18H16CL2N4O
Molecular Weight	375.251841545105
Exact Mass	374.07
CAS #	1508286-18-7
PubChem CID	122535411
Appearance	White to off-white solid powder
LogP	5.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	25
Complexity	618
Defined Atom Stereocenter Count	0
SMILES	ClC1C=C(C=C(C=1)C1(C(C#N)=C(N)OC2C1=C(C)NN=2)C1CCC1)Cl
InChi Key	SPNNZCKKJSFKKB-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H16Cl2N4O/c1-9-15-17(24-23-9)25-16(22)14(8-21)18(15,10-3-2-4-10)11-5-12(19)7-13(20)6-11/h5-7,10H,2-4,22H2,1H3,(H,23,24)
Chemical Name	6-amino-4-cyclobutyl-4-(3,5-dichlorophenyl)-3-methyl-2H-pyrano[2,3-c]pyrazole-5-carbonitrile
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

[1]. Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities. J Med Chem. 2015 Apr 9;58(7):3117-30.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~666.22 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6649 mL	13.3245 mL	26.6489 mL
	5 mM	0.5330 mL	2.6649 mL	5.3298 mL
	10 mM	0.2665 mL	1.3324 mL	2.6649 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.