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| Targets |
PIP-199 targets the FANCM-RMI protein-protein interaction within the RecQ-mediated genome instability pathway. The Fanconi anemia (FA) DNA repair pathway is a common mechanism by which tumors evolve resistance to DNA crosslinking chemotherapies. Proper execution of the FA pathway requires interaction between FANCM and the RMI complex. By disrupting this interaction, PIP-199 impairs FA pathway function, sensitizing cells to DNA-damaging agents and contributing to genomic instability in cancer cells.
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| ln Vitro |
Fanconi anemia complementation group M protein (FANCM) and the RMI complex bind to MM2 [1]. Tumors often develop resistance to DNA cross-linking treatment through induction of the Fanconi anemia (FA) DNA repair pathway [1]. FANCM and RMI complex interactions are necessary for the FA pathway to function properly, and mutations that impair these connections make cells more susceptible to DNA cross-linkers [1].
PIP-199 is a selective inhibitor of the RMI core complex/MM2 interaction with an IC50 of 36 μM. It demonstrates biochemical activity that is reported to be 12- to 37-fold weaker than ML216. The compound is used in DNA damage response research to study genome stability mechanisms. Induction of the Fanconi anemia DNA repair pathway is a common mechanism by which tumors evolve resistance to DNA crosslinking chemotherapies, and PIP-199 can sensitize resistant tumors to such agents. |
| ln Vivo |
In vivo activity data for PIP-199 are limited in the available literature. The compound is characterized as a research tool for studying DNA repair mechanisms and synthetic lethality in cancer cells. By disrupting the FANCM-RMI interaction, PIP-199 impairs the Fanconi anemia pathway and sensitizes cells to DNA-damaging agents. The compound can be used for the research of sensitizing resistant tumors to DNA crosslinking chemotherapeutics, though specific in vivo efficacy data are not detailed in the available sources.
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| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for PIP-199 are not extensively detailed. The compound inhibits the protein-protein interaction between the RMI core complex and MM2 with an IC50 of 36 μM. Binding affinity is determined using biochemical assays that measure disruption of the RMI-FANCM interaction. The compound’s biochemical activity is characterized through protein-protein interaction assays, likely using techniques such as fluorescence polarization, surface plasmon resonance, or AlphaScreen technology.
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| Cell Assay |
In vitro cell-based assays for PIP-199 involve treatment of cancer cell lines to assess sensitization to DNA crosslinking agents. Cells are treated with PIP-199 in combination with DNA-damaging agents such as cisplatin or mitomycin C, and cell viability is assessed using standard cytotoxicity assays. The compound’s effect on the Fanconi anemia pathway is evaluated by monitoring DNA repair efficiency and the formation of DNA damage foci using immunofluorescence microscopy.
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| Animal Protocol |
In vivo animal studies for PIP-199 are not detailed in the available literature. As a research compound targeting the Fanconi anemia DNA repair pathway, typical in vivo evaluation would involve xenograft mouse models to assess whether PIP-199 can sensitize tumors to DNA crosslinking chemotherapeutics. Tumor-bearing mice would be treated with PIP-199 in combination with DNA-damaging agents, and tumor growth inhibition would be monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PIP-199 are not extensively reported. The compound has a molecular formula of C27H28N4O3, a molecular weight of 456.54 g/mol, and a LogP of 4.3. It appears as a white to off-white solid powder. The compound contains one hydrogen bond donor and five hydrogen bond acceptors, with six rotatable bonds. Storage: powder at -20°C for 3 years or 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month.
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| Toxicity/Toxicokinetics |
Soluble in DMSO.
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| References | |
| Additional Infomation |
Toxicological data for PIP-199 are limited in the available literature. The compound is classified for research use only and is not intended for human therapeutic use. As an inhibitor of the Fanconi anemia DNA repair pathway, potential toxicities would relate to impaired DNA repair in normal tissues, though specific toxicity profiles are not detailed. The compound’s IC50 of 36 μM suggests moderate potency, and formal toxicological studies have not been reported in the available sources.
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| Molecular Formula |
C27H28N4O3
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| Molecular Weight |
456.536226272583
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| Exact Mass |
456.216
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| CAS # |
622795-76-0
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| PubChem CID |
4081132
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| Appearance |
White to off-white solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
664
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ON1C2C=CC=CC=2C(=C1C1C=CC=CC=1)C(C1C=CC=CN=1)N1CCN(C(=O)OCC)CC1
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| InChi Key |
ROTCTSYSZSYNHB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H28N4O3/c1-2-34-27(32)30-18-16-29(17-19-30)26(22-13-8-9-15-28-22)24-21-12-6-7-14-23(21)31(33)25(24)20-10-4-3-5-11-20/h3-15,26,33H,2,16-19H2,1H3
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| Chemical Name |
4-[(1-Hydroxy-2-phenyl-1H-indol-3-yl)-pyridin-2-yl-methyl]-piperazine-1-carboxylic acid ethyl ester
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| Synonyms |
PIP-199 PIP199 PIP 199
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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 : ~41.67 mg/mL (~91.27 mM)
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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 | 2.1904 mL | 10.9519 mL | 21.9039 mL | |
| 5 mM | 0.4381 mL | 2.1904 mL | 4.3808 mL | |
| 10 mM | 0.2190 mL | 1.0952 mL | 2.1904 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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