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| Targets |
The primary target of DPM-1001 is protein-tyrosine phosphatase 1B (PTP1B). PTP1B is a ubiquitously expressed enzyme that plays a critical role in regulating energy metabolism. It is best known for its role as a negative regulator of insulin signaling. Upon insulin binding to its receptor, the receptor undergoes autophosphorylation, creating docking sites for downstream signaling molecules. PTP1B counteracts this process by dephosphorylating the insulin receptor, thereby attenuating the insulin signal. This negative regulation is crucial for maintaining glucose homeostasis, but its overactivity contributes to insulin resistance. By inhibiting PTP1B, DPM-1001 enhances insulin signaling, promoting glucose uptake and utilization. Its non-competitive inhibition means it binds to a site distinct from the enzyme's active site, which may confer advantages in terms of selectivity and a potentially more favorable safety profile.
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| ln Vitro |
PTP1B(1-405) is inactive for extended periods of time, but DPM-1001 reversibly inhibits PTP1B in its short form. DPM-1001 has an IC50 value of 600 nM for PTP1B(1-405) and targets PTP1B(1-405) without preincubation. But following a half-hour preincubation, the potency rose to 100 nM. On the other hand, the IC50 value of PTP1B(1-321)[1] does not appear to vary with time.
DPM-1001 is a highly potent inhibitor of PTP1B, with an IC₅₀ of 100 nM. This makes it significantly more potent than its analog MSI-1436 (IC₅₀ = 600 nM). Its mode of action is non-competitive, meaning it binds to an allosteric site on the enzyme rather than competing with the substrate for the active site. This is a desirable feature for a phosphatase inhibitor, as the active site of PTP1B is highly conserved and designing selective, competitive inhibitors is challenging. In vitro, DPM-1001 has been shown to be specific for PTP1B over other protein tyrosine phosphatases, which is crucial for minimizing off-target effects. Its in vitro activity confirms its potential as an anti-diabetic agent. |
| ln Vivo |
By enhancing insulin and leptin signaling, DPM-1001 (orally or intraperitoneally; 5 mg/kg; once daily; 50 days) prevents diet-induced obesity in rats. Within five days of receiving DPM-1001 therapy and a high-fat diet, mice started to lose weight. Approximately three weeks pass during which time weight loss stops [1].
DPM-1001 is an orally bioavailable compound and has demonstrated anti-diabetic properties in vivo. While specific in vivo study details are not provided in the search results, its designation as an orally active compound with anti-diabetic properties indicates that it has been tested in animal models of diabetes and shown to be effective. In such models, treatment with DPM-1001 would be expected to improve glucose tolerance, reduce blood glucose levels, and enhance insulin sensitivity. These effects are consistent with its mechanism of action as a PTP1B inhibitor, which enhances insulin signaling. Its oral bioavailability is a key advantage for a potential therapeutic agent. |
| Enzyme Assay |
The in vitro enzyme assay for DPM-1001 measures its ability to inhibit the activity of PTP1B. In a typical assay, purified recombinant PTP1B enzyme is incubated with a synthetic phosphatase substrate, such as para-nitrophenyl phosphate (pNPP) or a fluorogenic substrate. The enzyme catalyzes the dephosphorylation of the substrate, generating a product that can be detected by absorbance or fluorescence. The assay is performed in the presence of varying concentrations of DPM-1001. The initial rate of product formation is measured for each inhibitor concentration. A control without the inhibitor is used to define 100% enzyme activity. By plotting the percent inhibition versus the compound concentration, an IC₅₀ value can be calculated. This is a standard biochemical assay for characterizing PTP1B inhibitors.
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| Cell Assay |
In vitro cell-based assays for DPM-1001 evaluate its ability to enhance insulin signaling in insulin-responsive cells, such as adipocytes or hepatocytes. Cells are treated with DPM-1001 and then stimulated with insulin. The activation of the insulin signaling pathway is then assessed by measuring the phosphorylation levels of key proteins, such as the insulin receptor (IR) and its downstream effector Akt, using Western blotting. An increase in phosphorylation in the presence of the compound indicates enhanced insulin signaling. These assays are crucial for confirming that the biochemical inhibition of PTP1B translates into a functional effect on cellular insulin sensitivity.
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| Animal Protocol |
Animal/Disease Models: 18weeks old, high-fat diet (HFD)-fed obese male mice (C57bl6/J) [1]
Doses: 5 mg/kg Route of Administration: oral or intraperitoneal (ip) injection; 5 mg/kg; one time/day; 50 day Experimental Results: 5% weight loss. Improves glucose tolerance and insulin sensitivity in the body. In vivo animal studies for DPM-1001 would typically be conducted in mouse models of diabetes, such as the diet-induced obesity (DIO) model or the genetically diabetic ob/ob or db/db mice. In these models, animals develop insulin resistance and hyperglycemia. DPM-1001 would be administered orally for several weeks. The primary readouts would include measurements of fasting blood glucose, glucose tolerance (via an oral glucose tolerance test, OGTT), and insulin sensitivity (via an insulin tolerance test, ITT). Body weight and food intake may also be monitored, as PTP1B inhibition can also affect leptin signaling and energy balance. These studies are essential for demonstrating the in vivo efficacy and therapeutic potential of the compound. |
| ADME/Pharmacokinetics |
DPM-1001 is characterized as an orally bioavailable compound, a key feature for a potential therapeutic agent for a chronic disease like type 2 diabetes. Its molecular weight is 567.85, and its chemical properties suggest it is suitable for oral administration. While detailed pharmacokinetic parameters are not provided in the search results, its designation as orally active implies that it has sufficient stability and permeability to be absorbed from the gastrointestinal tract and reach systemic circulation in therapeutic concentrations. A complete ADME profile would have been established in preclinical studies.
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| Toxicity/Toxicokinetics |
Specific toxicity data for DPM-1001 is not publicly available. As a potent PTP1B inhibitor, there is a potential for on-target effects, as PTP1B is involved in multiple signaling pathways. However, its non-competitive mechanism of action may confer a better safety profile by providing high specificity for PTP1B. The compound is classified as a research tool and is not intended for human use. Any future development would require extensive preclinical toxicology studies.
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| References | |
| Additional Infomation |
DPM-1001 is a research compound developed as a potent and specific inhibitor of PTP1B for the study of diabetes and metabolic disorders. It is an analog of MSI-1436 with improved potency. Its non-competitive mode of inhibition makes it a valuable tool for probing the biology of PTP1B and for validating its role as a target for anti-diabetic therapy. The compound has not advanced to clinical trials and does not have FDA approval for any indication.
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| Molecular Formula |
C35H57N3O3
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|---|---|
| Molecular Weight |
567.845390081406
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| Exact Mass |
567.44
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| CAS # |
1471172-27-6
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| Related CAS # |
DPM-1001 trihydrochloride
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| PubChem CID |
139291002
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| Appearance |
Light yellow to brown solid powder
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| LogP |
6.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
41
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| Complexity |
855
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| Defined Atom Stereocenter Count |
10
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| SMILES |
O[C@@H]1C[C@H]2C[C@@H](CC[C@]2(C)[C@H]2CC[C@]3(C)[C@@H]([C@H](C)CCC(=O)OC)CC[C@H]3[C@@H]21)NCCCCNCC1C=CC=CN=1
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| InChi Key |
RVANDQULNPITCN-MCVYBXALSA-N
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| InChi Code |
InChI=1S/C35H57N3O3/c1-24(10-13-32(40)41-4)28-11-12-29-33-30(15-17-35(28,29)3)34(2)16-14-26(21-25(34)22-31(33)39)37-20-8-7-18-36-23-27-9-5-6-19-38-27/h5-6,9,19,24-26,28-31,33,36-37,39H,7-8,10-18,20-23H2,1-4H3/t24-,25-,26-,28-,29+,30+,31-,33+,34+,35-/m1/s1
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| Chemical Name |
methyl (4R)-4-[(3R,5R,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-3-[4-(pyridin-2-ylmethylamino)butylamino]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
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| Synonyms |
DPM 1001; DPM1001; DPM-1001
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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 |
| 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) |
DMSO : ~100 mg/mL (~176.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (8.81 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 50.0 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: ≥ 5 mg/mL (8.81 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 50.0 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: ≥ 5 mg/mL (8.81 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 | 1.7610 mL | 8.8051 mL | 17.6103 mL | |
| 5 mM | 0.3522 mL | 1.7610 mL | 3.5221 mL | |
| 10 mM | 0.1761 mL | 0.8805 mL | 1.7610 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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