For research use only. Not for therapeutic Use.
SJG-136（Cat No.:I002776）is a synthetic small-molecule compound that acts as a DNA crosslinking agent, targeting guanine bases within the DNA helix. By forming covalent bonds with DNA, SJG-136 disrupts DNA replication and transcription, leading to cell cycle arrest and apoptosis in cancer cells. It has demonstrated potent activity against various malignancies, including those resistant to conventional therapies. SJG-136 is particularly noteworthy for its selectivity in targeting cancer cells over normal cells, making it a promising candidate in the development of novel cancer therapeutics, with ongoing research to optimize its efficacy and safety profile.
| Catalog Number | I002776 |
| CAS Number | 232931-57-6 |
| Molecular Formula | C31H32N4O6 |
| Purity | ≥95% |
| Target | DNA cross-linking |
| Solubility | 10 mM in DMSO |
| Storage | Store at -20°C |
| IC50 | 0.83 nM (TGI) |
| IUPAC Name | (6aS)-3-[3-[[(6aS)-2-methoxy-8-methylidene-11-oxo-7,9-dihydro-6aH-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-8-methylidene-7,9-dihydro-6aH-pyrrolo[2,1-c][1,4]benzodiazepin-11-one |
| InChI | InChI=1S/C31H32N4O6/c1-18-8-20-14-32-24-12-28(26(38-3)10-22(24)30(36)34(20)16-18)40-6-5-7-41-29-13-25-23(11-27(29)39-4)31(37)35-17-19(2)9-21(35)15-33-25/h10-15,20-21H,1-2,5-9,16-17H2,3-4H3/t20-,21-/m0/s1 |
| InChIKey | RWZVMMQNDHPRQD-SFTDATJTSA-N |
| SMILES | COC1=C(C=C2C(=C1)C(=O)N3CC(=C)C[C@H]3C=N2)OCCCOC4=C(C=C5C(=C4)N=C[C@@H]6CC(=C)CN6C5=O)OC |
| Reference | </br>1:Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours. Mellinas-Gomez M, Spanswick VJ, Paredes-Moscosso SR, Robson M, Pedley RB, Thurston DE, Baines SJ, Stell A, Hartley JA.BMC Vet Res. 2015 Aug 19;11:215. doi: 10.1186/s12917-015-0534-2. PMID: 26282406 Free PMC Article</br>2:γ-H2AX foci formation as a pharmacodynamic marker of DNA damage produced by DNA cross-linking agents: results from 2 phase I clinical trials of SJG-136 (SG2000). Wu J, Clingen PH, Spanswick VJ, Mellinas-Gomez M, Meyer T, Puzanov I, Jodrell D, Hochhauser D, Hartley JA.Clin Cancer Res. 2013 Feb 1;19(3):721-30. doi: 10.1158/1078-0432.CCR-12-2529. Epub 2012 Dec 18. PMID: 23251007 Free Article</br>3:Nuclear magnetic resonance solution structures of inter- and intrastrand adducts of DNA cross-linker SJG-136. Hopton SR, Thompson AS.Biochemistry. 2011 May 31;50(21):4720-32. doi: 10.1021/bi102017e. Epub 2011 May 3. PMID: 21488658 </br>4:Phase I pharmacokinetic and pharmacodynamic study of SJG-136, a novel DNA sequence selective minor groove cross-linking agent, in advanced solid tumors. Puzanov I, Lee W, Chen AP, Calcutt MW, Hachey DL, Vermeulen WL, Spanswick VJ, Liao CY, Hartley JA, Berlin JD, Rothenberg ML.Clin Cancer Res. 2011 Jun 1;17(11):3794-802. doi: 10.1158/1078-0432.CCR-10-2056. Epub 2011 Feb 23. PMID: 21346148 Free PMC Article</br>5:Pharmacokinetics, pharmacodynamics and metabolism of the dimeric pyrrolobenzodiazepine SJG-136 in rats. Reid JM, Buhrow SA, Kuffel MJ, Jia L, Spanswick VJ, Hartley JA, Thurston DE, Tomaszewski JE, Ames MM.Cancer Chemother Pharmacol. 2011 Sep;68(3):777-86. doi: 10.1007/s00280-010-1517-4. Epub 2010 Dec 28. PMID: 21188379 </br>6:The pyrrolobenzodiazepine dimer SJG-136 forms sequence-dependent intrastrand DNA cross-links and monoalkylated adducts in addition to interstrand cross-links. Rahman KM, Thompson AS, James CH, Narayanaswamy M, Thurston DE.J Am Chem Soc. 2009 Sep 30;131(38):13756-66. doi: 10.1021/ja902986x. PMID: 19725510 </br>7:A phase I trial of SJG-136 (NSC#694501) in advanced solid tumors. Janjigian YY, Lee W, Kris MG, Miller VA, Krug LM, Azzoli CG, Senturk E, Calcutt MW, Rizvi NA.Cancer Chemother Pharmacol. 2010 Apr;65(5):833-8. doi: 10.1007/s00280-009-1088-4. Epub 2009 Aug 12. PMID: 19672598 Free PMC Article</br>8:Phase I study of sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors. Hochhauser D, Meyer T, Spanswick VJ, Wu J, Clingen PH, Loadman P, Cobb M, Gumbrell L, Begent RH, Hartley JA, Jodrell D.Clin Cancer Res. 2009 Mar 15;15(6):2140-7. doi: 10.1158/1078-0432.CCR-08-1315. Epub 2009 Mar 10. PMID: 19276288 Free Article</br>9:Cloning and characterization of the biosynthetic gene cluster for tomaymycin, an SJG-136 monomeric analog. Li W, Chou S, Khullar A, Gerratana B.Appl Environ Microbiol. 2009 May;75(9):2958-63. doi: 10.1128/AEM.02325-08. Epub 2009 Mar 6. PMID: 19270147 Free PMC Article</br>10:Determination of chemically reduced pyrrolobenzodiazepine SJG-136 in human plasma by HPLC-MS/MS: application to an anticancer phase I dose escalation study. Wade Calcutt M, Lee W, Puzanov I, Rothenberg ML, Hachey DL.J Mass Spectrom. 2008 Jan;43(1):42-52. PMID: 17683023 |
