RKS262
RKS262 is an orally active cyclin/CDK inhibitor. RKS262 is also an apoptosis inducer and cell cycle regulator, exhibiting cytotoxic activity against cancer cells. RKS262 induces caspase-3 cleavage, ROS generation, SAPK/JNK activation, and upregulates the expression of p53, Bid, Bad, Bok, and p27. RKS262 inhibits the expression of Bcl-2, Mcl-1, Bcl-xL, p21, cyclin D1, cyclin B1, cdc-2, cyclin D4, and DNA-pk KU-80 subunit. RKS262 suppresses the phosphorylation of the IGF-1R/PI3K/PKC pathway, ras oncogene activity, and Cdk-6, while increasing total Akt expression. RKS262 induces G2/M or S phase cell cycle arrest, disrupts mitochondrial transmembrane potential, and reduces tumor burden in xenograft models. RKS262 is used in research on neuroblastoma and ovarian cancer.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- CAS. Nr.: 1041469-97-9
- Formel: C15H14BrClN2O4S
- Molecular Weight:433.70
-
Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biologische Aktivität
-
Chemical Information
- Reinheit & Dokumentation
- Verweise
-
Help & FAQs
Alle Caspase Isoform-spezifische Produkte anzeigen
More
Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
CDK6 |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| BE(2)-C | IC50 |
10.23 μM
|
Antiproliferative activity against human Be(2)C neuroblastoma cells assessed as reduction in cell viability incubated for 48 hrs by Calcein AM assay.
Antiproliferative activity against human Be(2)C neuroblastoma cells assessed as reduction in cell viability incubated for 48 hrs by Calcein AM assay.
|
21532338 |
| SH-SY5Y | IC50 |
7.12 μM
|
Antiproliferative activity against human SHSY5Y neuroblastoma cells assessed as reduction in cell viability incubated for 48 hrs by Calcein AM assay.
Antiproliferative activity against human SHSY5Y neuroblastoma cells assessed as reduction in cell viability incubated for 48 hrs by Calcein AM assay.
|
21532338 |
| OVCAR-3 | IC50 |
3 μM
|
Cytotoxicity against human ovarian epithelial adenocarcinoma OVCAR-3 cells assessed via cell-cycle analysis by flow cytometry after 24 h treatment.
Cytotoxicity against human ovarian epithelial adenocarcinoma OVCAR-3 cells assessed via cell-cycle analysis by flow cytometry after 24 h treatment.
|
19865799 |
In Vitro
RKS262 (0-50 μM; 48 h) potently inhibits the growth of Be (2) C, CHLA-90, LA1-55n, LAN-2, SMSKCNR, and SHSY5Y neuroblastoma cell lines in vitro, with IC50 values ranging from 6.97 μM to 24.3 μM[1].
RKS262 (10 nM-100 μM) potently inhibits the growth of most NCI-60 human cancer cell lines, with leukemia cell lines being the most sensitive (GI50 of 10 nM), whereas some non-small cell lung, breast, central nervous system, melanoma, renal, and ovarian cancer cell lines are relatively resistant (GI50 >1 μM); in a panel of ovarian cancer cell lines treated at 100 nM or 100 μM, this compound exhibits dose-dependent growth inhibition[2].
RKS262 (5 μM; 48 h) exhibits high cytotoxicity against human ovarian cancer cells OVCAR-3[2].
RKS262 (5 μM; 1-36 h) modulates key oncogenic and signaling pathways in human ovarian cancer cells OVCAR-3: it inhibits ras within 1 h, downregulates DNA-pk KU-80 in a time-dependent manner (starting at 6 h and reaching background levels by 18 h), and, during 36 h of treatment at 5 μM, first induces Akt phosphorylation and activation, followed by its downregulation (with a concurrent increase in total Akt expression)[2].
RKS262 (11 μM; 15 h) induces DNA fragmentation and apoptotic/necrotic cell death in SMSKCNR neuroblastoma cells[1].
RKS262 (7 μM; 4-24 h) activates SAPK/JNK and caspase-3, cleaves PARP-1, and inhibits IGF-1R/PI3K/PKC phosphorylation in SMSKCNR neuroblastoma cells; pretreatment with 100 μM ascorbic acid or 20 μM SB203580 (HY-10256) reverses these effects[1].
RKS262 (7 μM; 4-24 h) inhibits anti-apoptotic Bcl-2 family proteins (Mcl-1, Bcl-xL, phosphorylated Bcl-2) in SMSKCNR neuroblastoma cells, and pretreatment with 20 μM SB203580 reverses its inhibitory effect on phosphorylated Bcl-2[1].
RKS262 (11.5-50 μM; 30 min) induces dose-dependent ROS generation in LA1-55n, SMSKCNR, and SHSY5Y neuroblastoma cells[1].
RKS262 (23 μM; 24 h) exhibits reduced cytotoxicity in SMSKCNR neuroblastoma cells pretreated with 10 mM N-Acetylcysteine amide (NAC) (HY-110256) for 3 h[1].
RKS262 (7 μM; 24 h) induces G2/M phase arrest and downregulates the expression of cdc2, cyclin B1, p21, cyclin D1, and cyclin D4, while upregulating p53 expression; pretreatment with 100 μM ascorbic acid or 20 μM SB203580 partially reverses these effects[1].
RKS262 (5-7 μM; 4-24 h) reverses the activation state of SAPK/JNK or ROS in SMSKCNR neuroblastoma cells pretreated with exogenous BDNF; when treated with 7 μM RKS262 for 24 h, co-treatment with BDNF, EGF, or IGF-1 shifts RKS262-induced cell cycle arrest from the G2/M phase to the S phase[1].
RKS262 (5 μM; 12 h) disrupts the mitochondrial membrane potential in human ovarian cancer OVCAR-3 cells, leading to the loss of ΔYm[2].
RKS262 (1-3 μM; 24 h) arrests the cell cycle progression of human ovarian cancer OVCAR-3 cells at the G2/M phase[2].
RKS262 (5 μM; 24 h) regulates the expression of cell cycle regulatory proteins in human ovarian cancer OVCAR-3 cells, upregulating p27 expression and downregulating cyclin D1 and CDK-6 expression, without altering the levels of p21 or p16[2].
RKS262 (5 μM; 1-18 h) induces apoptosis in human ovarian cancer OVCAR-3 cells, activates caspase-3 and caspase-7, and cleaves PARP-1[2].
RKS262 (5 μM; 1-36 h) selectively modulates the expression of Bcl2 family proteins in human ovarian cancer OVCAR-3 cells: it activates pro-apoptotic proteins Bid and Bad within 1 h, upregulates pro-apoptotic protein Bok at 36 h, downregulates anti-apoptotic proteins Bcl-xl and Mcl-1 within 6 h under 5 μM treatment, and does not alter the expression levels of Bax or Bak[2].
RKS262 (3 μM) induces apoptosis by regulating Bcl-2 family proteins and mitochondrial depolarization, exhibiting strong cytotoxicity in human ovarian cancer OVCAR-3 cells, with its activity correlated with RAS oncogene status[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:Be(2)C, CHLA-90, LA1-55n, LAN-2, SMSKCNR, SHSY5Y human neuroblastoma cell lines
-
Concentration:0, 11.5, 23, 50 μM
-
Incubation Time:48 h
-
Result:Inhibited cell growth in a concentration-dependent manner across all six cell lines.
Reduced surviving cells to 5-10% in all cell lines at 23 or 50 μM.
Achieved IC50 values of 10.23 μM (Be(2)C), 21.47 μM (CHLA-90), 24.3 μM (LA1-55n), 6.97 μM (LAN-2), 7.32 μM (SMSKCNR), and 7.12 μM (SHSY5Y).
-
Cell Line:SMSKCNR human neuroblastoma cells
-
Concentration:11 μM
-
Incubation Time:15 h
-
Result:Induced a significant number of TUNEL-positive nuclei compared to vehicle controls.
-
Cell Line:SMSKCNR human neuroblastoma cells
-
Concentration:7 μM (RKS262); 100 μM (ascorbic acid pre-treatment); 20 μM (SB203580 pre-treatment)
-
Incubation Time:4-24 h (RKS262); 1 h (ascorbic acid/SB203580 pre-treatment)
-
Result:Caused strong, sustained activation of phosphorylated SAPK/JNK between 4 and 12h, but not at 24h.
Induced time-dependent cleavage of caspase-3 increasing over 4, 12, 24h.
Induced PARP-1 cleavage at 12 and 24h.
Suppressed phosphorylation of IGF-1R, PI3K, and PKC between 12 and 24h.
Suppressed phosphorylated SAPK/JNK and reduced cleaved caspase-3 levels at 24h with pre-treatment of ascorbic acid or SB203580.
Reversed suppression of IGF-1R/PI3K/PKC phosphorylation with pre-treatment of ascorbic acid or SB203580.\nSuppressed expression of anti-apoptotic Bcl-2 family members Mcl-1, Bcl-xL, and phospho-Bcl-2.
Left pro-apoptotic Bax and Bid levels unchanged.
Reversed RKS262-induced suppression of phospho-Bcl-2 with pre-treatment of SB203580, but not ascorbic acid.
-
Cell Line:SMSKCNR human neuroblastoma cells
-
Concentration:7 μM (RKS262); 100 μM (ascorbic acid pre-treatment); 20 μM (SB203580 pre-treatment)
-
Incubation Time:24 h (RKS262); 1 h (ascorbic acid/SB203580 pre-treatment)
-
Result:Increased the G2/M-phase cell population to ~50% and reduced the G1-phase population compared to vehicle controls, with S-phase population largely unchanged.
Induced time-dependent downregulation of cdc2, cyclin B1, p21, cyclin D1, and cyclin D4, and upregulation of p53 between 4 and 24h.
Reversed suppression of cdc2, cyclin B1, and cyclin D4 with pre-treatment of ascorbic acid or SB203580.
Halted p53 activation with pre-treatment of ascorbic acid.
-
Cell Line:human ovarian epithelial adenocarcinoma OVCAR-3 cells
-
Concentration:1 μM, 3 μM
-
Incubation Time:24 h
-
Result:Caused significant increase in G2/M-phase cell population and reduction in G1-phase cell population compared to untreated controls.
Induced a G2/M-phase cell-cycle block within 24 h of treatment.
-
Cell Line:human ovarian epithelial adenocarcinoma OVCAR-3 cells
-
Concentration:5 μM
-
Incubation Time:1 h, 18 h
-
Result:Activated/cleaved executioner caspase-3 and caspase-7 within 1 h, with maximal activation at 18 h.
Induced cleavage of PARP-1 within 1 h of treatment, a marker of apoptotic cell disassembly.\nCaused only minor upregulation/activation of SAP/JNK and p38 MAPK.
Indicated induced cytotoxicity is mainly independent of these proapoptotic MAPKs.
-
Cell Line:human ovarian epithelial adenocarcinoma OVCAR-3 cells
-
Concentration:5 μM
-
Incubation Time:1 h, 6 h, 18 h, 36 h
-
Result:Exerted strong inhibitory effects on oncogene ras within 1 h of treatment.
Initially upregulated DNA-pk KU-80 subunit expression, then down-regulated KU-80 to background levels by 18 h, with down-regulation beginning at 6 h.
Activated Akt within 1 h, then down-regulated Akt phosphorylation to background levels by 36 h, with cells counteracting this by increasing Akt expression over time.
-
Cell Line:human ovarian epithelial adenocarcinoma OVCAR-3 cells
-
Concentration:5 μM
-
Incubation Time:1 h, 6 h, 36 h
-
Result:Caused strong, rapid (within 1 h), and sustained (up to 36 h) activation of pro-apoptotic Bid and Bad.
Up-regulated pro-apoptotic Bok after 36 h.
Left levels of pro-apoptotic Bax and Bak unchanged.
Strongly down-regulated expression of anti-apoptotic Bcl-xl and Mcl-1 within 6 h of treatment.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Crl:NU-Foxn1^nu (female, 6 weeks old, subcutaneous xenograft via flank injection of 1 × 107 SMSKCNR cells suspended in Matrigel)[1]
-
Dosage:150 mg/kg
-
Administration:p.o.; daily; 28 days
-
Result:Reduced average tumor volume from 2.35 cm3 to 0.967 cm3, representing a 60% reduction in tumor burden.
Showed no ulcer formation at the tumor site, secondary pathological conditions, changes in behavior, average weight, or toxicity.
Chemical Information
-
CAS. Nr. 1041469-97-9
-
Molecular Weight 433.70
-
Formel C15H14BrClN2O4S
-
SMILES
O=C1OC2=C(C(Cl)=C1/C=N/N3CCS(=O)(CC3C)=O)C=C(Br)C=C2
-
Versand
Room temperature in continental US; may vary elsewhere.
-
Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
RKS262 Related Classifications
HY-113720 Related Classifications
Powered by Bioz