| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
pKi: 7.6 (MCT-1) and 6.6 (MCT-2)[1]
AR-C141990 hydrochloride specifically targets the monocarboxylate transporter 1 (MCT1, also known as SLC16A1). It acts as a selective inhibitor, demonstrating a pKi value of 7.6 for MCT1, which translates to a Ki value of approximately 25 nM. It also shows affinity for MCT2 (pKi = 6.6; Ki ≈ 250 nM), indicating it has approximately 10-fold selectivity for MCT1 over MCT2. It has no significant activity against MCT3 or MCT4, making it a selective MCT1 inhibitor.. |
|---|---|
| ln Vitro |
There is no discernible efficacy of AR-C141990 hydrochloride against MCT-3 (pIC50<5) or MCT-4 (pIC50<5)[1]. With IC50s of 0.21 µM and 2.32 µM, respectively, AR-C141990 hydrochloride reduces the absorption of [3H]HOCPCA in oocytes expressing MCT1 or 2 in a concentration-dependent manner[2].
In vitro, AR-C141990 hydrochloride is a potent MCT1 inhibitor with a pKi of 7.6. It exhibits approximately 10-fold selectivity for MCT1 over MCT2 and no significant activity against MCT3 or MCT4.. This compound is designed to inhibit the import of lactate and other monocarboxylates into cells, which is a key metabolic pathway for cancer cells that rely on oxidative metabolism. |
| ln Vivo |
In male NMRI mice (18-22 g), AR-C141990 hydrochloride (10 mg/kg; SC) has a half-life of around 20 minutes and decreases in plasma concentrations concurrently [2]. The use of AR-C141990 hydrochloride at relevant plasma concentrations (0.3-90 mg/kg) causes a concentration-dependent reduction in HOCPCA's B/P, with an EC50 of 860 ng/ml[2]. In PVG rats receiving DA heart transplants, AR-C141990 (100 mg/kg; sc) exhibits a moderate extension of graft survival for 40 days[1].
Specific in vivo activity data for AR-C141990 hydrochloride has not been detailed in the provided search results. As a potent and selective MCT1 inhibitor, it is hypothesized to suppress tumor growth in animal models of cancer (e.g., xenograft models) where the cancer cells express high levels of MCT1. By blocking lactate import, the compound would deprive the tumor of a critical fuel source, potentially leading to reduced proliferation and necrosis. It may also be studied in models of exercise physiology or neurobiology due to the role of MCTs in lactate shuttling. |
| Enzyme Assay |
The standard in vitro protocol for MCT inhibition is a radiolabeled substrate uptake assay using cells expressing the specific MCT isoforms. HEK-293 cells stably expressing human MCT1 (and its ancillary protein CD147, which is required for surface trafficking) are seeded in 24-well plates. After reaching confluency, the cells are washed and pre-incubated with varying concentrations of AR-C141990 hydrochloride (0.1-10000 nM) in assay buffer (20 mM HEPES, pH 7.4, 5 mM KCl, 1 mM MgSO4, 1 mM CaCl2, 140 mM NaCl) for 15 minutes. The reaction is initiated by adding 100 uM of L-[14C]-lactic acid (1 uCi/mL) and incubated for 2-5 minutes. The uptake is terminated by washing the cells three times with ice-cold PBS containing 0.1 mM of a non-specific MCT inhibitor (e.g., AR-C155858). The cells are lysed with 0.2 N NaOH, and the radioactivity is counted. The pKi (7.6) is calculated by converting the Ki value derived from the inhibition curve.
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| Cell Assay |
The in vitro cellular assay for AR-C141990 hydrochloride involves the use of cancer cell lines that are known to be highly dependent on lactate import for survival and proliferation, such as the human colon cancer cell line HCT-116 or the breast cancer cell line MCF-7 (which rely on oxidative metabolism). Cells are seeded in 96-well plates and cultured in glucose-free medium containing 10 mM lactate as the primary carbon source. Varying concentrations of AR-C141990 hydrochloride (0.01-10000 nM) are added to the cells for 48-72 hours. Cell viability is measured using a standard MTT assay or CellTiter-Glo assay. The reduction in viability indicates the degree of metabolic reliance on MCT1-mediated lactate import. Alternatively, extracellular lactate levels in the culture medium can be measured using a lactate assay kit.
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| Animal Protocol |
An in vivo protocol for AR-C141990 hydrochloride would involve a subcutaneous xenograft model of a cancer known to rely on MCT1. For example, female BALB/c nude mice are inoculated with HCT-116 colon cancer cells. When tumors reach an average volume of 150-200 mm3, mice are randomized into groups. AR-C141990 hydrochloride is formulated in a suitable vehicle (e.g., 10% DMSO/40% PEG300/5% Tween-80/45% saline) and administered orally (PO) by gavage at doses of 10, 30, and 100 mg/kg, twice daily (BID). Tumor volumes are measured twice weekly with calipers. Tumor tissues are harvested at the end of the study and analyzed for ATP levels, lactate concentration, and markers of apoptosis (e.g., cleaved caspase-3 by Western blotting or immunohistochemistry). The primary endpoint is the reduction in tumor volume. AR-C141990 is selective for MCT1, so it would be active only in tumors that do not upregulate MCT4 as a compensatory mechanism.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for AR-C141990 hydrochloride is not provided. As a small molecule with a molecular weight of 529.05 g/mol, it is likely designed for oral administration.. A standard PK study in mice would involve oral (PO) administration (10 mg/kg) and intravenous (IV) administration (1 mg/kg). Serial blood samples are collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose. Plasma concentrations of the compound are quantified by LC-MS/MS. Key parameters, including terminal half-life (T1/2), maximum plasma concentration (Cmax), area under the curve (AUC), and oral bioavailability (F%), would be calculated. The compound is likely metabolized by the liver.
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| Toxicity/Toxicokinetics |
Specific toxicological data for AR-C141990 hydrochloride is not available. As an MCT1 inhibitor, the primary safety concern is the potential for lactic acidosis, particularly in the brain and heart, as these organs use lactate as a fuel source. Additionally, MCT1 is highly expressed on the basolateral membrane of intestinal epithelial cells, and inhibition could cause diarrhea or malabsorption. Standard safety assessment would include a 14-day repeat-dose oral toxicity study in rats to determine the Maximum Tolerated Dose (MTD) and the No-Observed-Adverse-Effect Level (NOAEL). Key endpoints would include monitoring of serum lactate and pH levels, neurological assessments (to detect CNS toxicity), and histopathological examination of the heart, brain, and intestine.
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| References |
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| Additional Infomation |
AR-C141990 hydrochloride is a research-grade chemical and is not approved for clinical use. It is a potent and selective inhibitor of the monocarboxylate transporter 1 (MCT1), a protein responsible for the import of lactate into cells. Its selectivity for MCT1 over MCT2 (10-fold) and MCT3/4 (inactive) makes it a valuable tool for studying the role of lactate transport in cancer metabolism, exercise physiology, and neurobiology. It is for research use only.
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| Molecular Formula |
C26H29CLN4O4S
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|---|---|
| Molecular Weight |
529.050863981247
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| Exact Mass |
528.159
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| CAS # |
2250019-94-2
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| Related CAS # |
AR-C141990;873327-59-4
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| PubChem CID |
129316183
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
840
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| Defined Atom Stereocenter Count |
1
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| SMILES |
Cl.S1C(CC2C=CN=C3C=CC=CC=23)=C(C2C(N(C)C(N(CC(C)C)C1=2)=O)=O)C(N1CC[C@H](C1)O)=O
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| InChi Key |
NFFGLQDNUHBVEY-UNTBIKODSA-N
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| InChi Code |
InChI=1S/C26H28N4O4S.ClH/c1-15(2)13-30-25-22(23(32)28(3)26(30)34)21(24(33)29-11-9-17(31)14-29)20(35-25)12-16-8-10-27-19-7-5-4-6-18(16)19;/h4-8,10,15,17,31H,9,11-14H2,1-3H3;1H/t17-;/m1./s1
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| Chemical Name |
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-1-(2-methylpropyl)-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8902 mL | 9.4509 mL | 18.9018 mL | |
| 5 mM | 0.3780 mL | 1.8902 mL | 3.7804 mL | |
| 10 mM | 0.1890 mL | 0.9451 mL | 1.8902 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.
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