| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
SC10914 targets PARP1, a key enzyme in the DNA repair pathway of base excision repair (BER). By inhibiting PARP1, it prevents the repair of single-strand breaks, leading to the accumulation of double-strand breaks during replication, which is particularly lethal to cells with deficient homologous recombination repair (HRR), such as BRCA1/2-deficient cells. This mechanism of synthetic lethality is the basis for its potent anti-tumor activity.
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| ln Vitro |
In vitro, SC10914 shows strong anti-proliferative activity against human BRCA1-deficient (MDA-MB-436, IC50 = 4.03 nM) and BRCA2-deficient (Capan-1, IC50 = 11.66 nM) tumor cells. It is also active against PTEN-deficient tumor cells (HGC-27, IC50 = 0.35 µM). These activities are consistent with its mechanism of PARP inhibition. The compound's high potency in these cell lines underscores its potential as an effective anticancer agent.
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| ln Vivo |
SC10914 is a highly potent PARP inhibitor (PARP1 IC50 = 7.87 nM) with potent anti-proliferative activity against human BRCA deficient tumor cells (MDA-MB-436, BRCA1 deficient, IC50 = 4.03 nM, Capan-1 BRCA2 deficient, IC50 = 11.66 nM) and PTEN deficient tumor cells (HGC-27,PTEN deficient, IC50 = 0.35 μM).[1]
In vivo, SC10914 demonstrates potent anti-tumor activity in BRCA1/2 mutant tumor models. Its favorable pharmacokinetic profile supports its potential as a clinical candidate for the treatment of BRCA1/2-deficient cancers. Studies have shown that SC10914 has better pharmacokinetic profiles compared to other PARP inhibitors. |
| Enzyme Assay |
The in vitro enzyme assay for SC10914 measures its inhibition of PARP1 enzymatic activity. The compound is incubated with purified PARP1 enzyme and a substrate. The IC50 value of 7.87 nM is determined by assessing the degree of inhibition. This assay allows for the direct quantification of the compound's potency against its primary target.
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| Cell Assay |
Cells (e.g., MDA-MB-436, Capan-1, HGC-27) are cultured and treated with varying concentrations of SC10914. Cell proliferation is measured after a defined period using assays such as CellTiter-Glo. The IC50 values for cell growth inhibition are calculated. These cellular assays confirm the compound's mechanism of action and its efficacy in a relevant biological context.
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| Animal Protocol |
Fragments of MDA-MB-436 tumor (approximately 1.5mm3) were implanted into the flank of female BALB/cA nude-mice which were randomized into four groups. Oral treatment with vehicle only, AZD2281 (75 mg/kg qd), SC10914 (25 mg/kg qd) or SC10914 (75 mg/kg qd) were carried out for 21 days. Vc8 xenograft was derived from Chinese hamster Vc8 (BRCA2 deficient) cells, fragments of Vc8 tumor (approximately 1.5mm3) were implanted into the flank of female BALB/cA nude-mice which were randomized into four groups; oral treatment with vehicle only, SC10914 (75 mg/kg qd), SC10914 (25 mg/kg qd) or SC10914 (5 mg/kg qd) were carried out for 21 days. SC10914 showed convincing in vivo efficacy at tolerated doses and resulted in robust dose-dependent anti-tumor efficacy in two xenograft models in nude-mice. Once daily oral treatment of SC10914 led to completed tumor stasis in established MDA-MB-436 xenografts and Vc-8 xenografts. In MDA-MB-436 xenografts, the low dose group (25mg/Kg) had the same efficacy with AZD2281 control group (75mg/Kg). SC10914 displayed a better pharmacokinetics profile compared with AZD2281 on SD rats with a single dosage of 15mg/Kg (oral bioavailability (%): 45.6% vs 26.2%, AUCinf (ng/mL/h): 3123 vs 1721, T1/2 (min): 160 vs 63.6). The pharmacokinetics profile displayed a positive correlation between the dosage of SC10914, drug plasma exposure (AUC0-t) and peak concentration (Cmax) when the dosages were in the range of 40-400mg/Kg. SC10914 has no hERG inhibition (IC50 > 30 μM). Ames tests suggested SC10914 has no mutagenic effects which were carried out in Salmonella typhimurium strains TA98 and TA100.
The in vivo efficacy of SC10914 is evaluated in mouse xenograft models. Mice bearing BRCA1/2-deficient tumors are treated with SC10914, and tumor growth is monitored. Endpoints such as tumor growth inhibition (TGI) are measured to assess the compound's antitumor activity. These studies have demonstrated that SC10914 shows potent anti-tumor activity. |
| ADME/Pharmacokinetics |
SC10914 possesses favorable pharmacokinetic properties. In a Phase I study, the half-life of SC10914 was about 2-5 hours. The exposure of SC10914 was increased with dose increasing at the dose of 30 mg to 250 mg. Its favorable pharmacokinetic profile is a key factor in its potential selection as a clinical candidate.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies would be conducted to evaluate the safety profile of SC10914. These would typically include assessments of body weight, clinical observations, hematology, clinical chemistry, and histopathology in relevant animal models. In a Phase I study, the main toxicity was blood-related adverse reactions.
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| References | |
| Additional Infomation |
SC10914 is a potent PARP inhibitor with a strong preclinical profile. Its significant activity against BRCA- and PTEN-deficient tumor cells, combined with favorable pharmacokinetics, positions it as a promising candidate for the treatment of cancers with defects in DNA repair pathways. A Phase I study has been conducted to assess the safety, tolerability, pharmacokinetics/pharmacodynamics and preliminary efficacy of SC10914 in patients with advanced solid tumors.
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| Molecular Formula |
C15H15NO2
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| Molecular Weight |
241.2851
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| Exact Mass |
241.11
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| Elemental Analysis |
C, 74.67; H, 6.27; N, 5.81; O, 13.26
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| CAS # |
76985-08-5
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| Related CAS # |
76985-08-5;63024-23-7 (HCl);155760-02-4 (S-isomer);170080-13-4 (R-isomer); 63087-78-5 (S-isomer HCl); 2159063-18-8 (R-isomer HCl);
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| PubChem CID |
11161741
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| Appearance |
Solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
428.6±40.0 °C at 760 mmHg
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| Flash Point |
213.0±27.3 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.608
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| LogP |
2.87
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
18
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| Complexity |
266
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C(C([H])(C([H])([H])C1C([H])=C([H])C(C2C([H])=C([H])C([H])=C([H])C=2[H])=C([H])C=1[H])N([H])[H])=O
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| InChi Key |
JCZLABDVDPYLRZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H15NO2/c16-14(15(17)18)10-11-6-8-13(9-7-11)12-4-2-1-3-5-12/h1-9,14H,10,16H2,(H,17,18)
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| Chemical Name |
2-amino-3-(4-phenylphenyl)propanoic acid
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| Synonyms |
SC-10914; SC 10914; SC10914;
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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) |
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 | 4.1444 mL | 20.7220 mL | 41.4439 mL | |
| 5 mM | 0.8289 mL | 4.1444 mL | 8.2888 mL | |
| 10 mM | 0.4144 mL | 2.0722 mL | 4.1444 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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