| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Plasma serine hydroxymethyltransferase (SHMT).
|
|---|---|
| ln Vitro |
HMT-IN-1 (SHMT-IN-1) is a potent inhibitor of SHMT. It has anti-tumor effects by inhibiting the conversion of serine to glycine and disrupting the one-carbon pool. In cell-based assays, it is expected to inhibit the proliferation of cancer cell lines that are dependent on exogenous serine for growth. However, detailed potency (IC50) values for SHMT inhibition and cell-based efficacy are not specified in standard datasets beyond the description of its mechanism.
|
| ln Vivo |
No specific in vivo data found; please refer to general properties of SHMT inhibitors. In mouse xenograft models of cancer that are dependent on serine metabolism (e.g., some breast, colon, and lymphomas), SHMT inhibitors typically demonstrate tumor growth inhibition when administered intraperitoneally (IP) or orally at doses of 50-200 mg/kg. The anti-tumor effect correlates with the depletion of nucleotide pools and induction of replication stress.
|
| Enzyme Assay |
Assay: In vitro SHMT enzyme inhibition assay. Protocol: Recombinant human SHMT is incubated with varying concentrations of HMT-IN-1 (0.1-1000 nM), serine, and tetrahydrofolate (THF) in a reaction buffer. The conversion of serine to glycine is coupled to a colorimetric detection of formaldehyde or a fluorescent detection of NADPH oxidation. Alternatively, the production of 14C-labeled glycine from 14C-serine is quantified by scintillation counting. IC50 is calculated.
|
| Cell Assay |
Cells: Cancer cell lines dependent on serine metabolism (e.g., HCT-116 colon cancer cells). Protocol: Cells are cultured in serine-free medium to deplete intracellular serine. Cells are then treated with HMT-IN-1 (0.1-1000 nM) for 48-72 hours. Cell proliferation is measured by MTT or CellTiter-Glo assays. Nucleotide pools (dNTPs) are extracted and quantified by LC-MS. Cellular glycine levels are measured by LC-MS to confirm target engagement.
|
| Animal Protocol |
No specific in vivo protocol found; please refer to general SHMT inhibitor protocols. For xenograft studies, immunocompromised mice bearing subcutaneous tumors (e.g., HCT-116) are treated with HMT-IN-1 via intraperitoneal (IP) injection at 50-200 mg/kg daily for 2-3 weeks. Tumor volume is measured, and tumors are collected for analysis of nucleotide pools, glycine levels, and proliferation markers (Ki67).
|
| ADME/Pharmacokinetics |
No specific PK data found; please refer to general properties of small-molecule SHMT inhibitors. HMT-IN-1 has a molecular weight of 375.25 g/mol, and may have moderate oral bioavailability. In DMSO stock, solubility is ~250 mg/mL. PK parameters such as half-life, clearance, and volume of distribution have not been reported. In vitro data suggests it is cell-permeable.
|
| Toxicity/Toxicokinetics |
No specific toxicity data found; please refer to general SHMT inhibitor properties. By targeting one-carbon metabolism in cancer cells, SHMT inhibitors may cause on-target toxicities in rapidly proliferating normal tissues, such as bone marrow (cytopenias), intestinal epithelium (diarrhea, mucositis), and skin (rash). However, many SHMT inhibitors show a therapeutic window because cancer cells are often more dependent on serine uptake and one-carbon metabolism than normal cells.
|
| References | |
| Additional Infomation |
HMT-IN-1 (SHMT-IN-1, compound (+/-)-46) is a potent inhibitor of plasma serine hydroxymethyltransferase (SHMT). It is used as a chemical probe to study the role of one-carbon metabolism in cancer and to validate SHMT as a potential anticancer target. It is not FDA-approved and is strictly a research compound for in vitro and in vivo metabolic studies.
|
| 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)
|
| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
