SJG-136 (NSC694501), a novel sequence-selective pyrrolobenzodiazepine (PBD) dimer, is a novel and potent DNA cross-linking/intercalating agent with an XL50 of 45 nM for pBR322 DNA; SJG-136 has potent anticancer activity and can be potentially used for the treatment of ovarian cancer and leukemia.

Physicochemical Properties

Molecular Formula	C31H32N4O6
Molecular Weight	556.6090
Exact Mass	556.232
CAS #	232931-57-6
PubChem CID	393111
Appearance	Off-white to yellow solid powder
Density	1.36g/cm3
Boiling Point	805.5ºC at 760 mmHg
Flash Point	441ºC
Vapour Pressure	5.52E-26mmHg at 25°C
Index of Refraction	1.66
LogP	3.271
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	8
Heavy Atom Count	41
Complexity	1020
Defined Atom Stereocenter Count	2
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
InChi Key	RWZVMMQNDHPRQD-SFTDATJTSA-N
InChi Code	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
Chemical 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
Synonyms	SJG-136; NSC-694501; SJG136; NSC694501; SJG 136; NSC 694501;
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	DNA cross-linker SJG-136 (dimer 5) has an XL50 (reagent concentration needed for 50% cross-linking of pBR322 DNA) of 45 nM. A2780 (IC50, 22.5 pM), A2780cisR (IC50, 24 pM), CH1 (IC50, 0.12 nM), CH1cisR (IC50, 0.6 nM), and SKOV-3 (IC50, 9.1 nM) are among the ovarian cell lines that are cytotoxic to SJG-136 [1]. A set of canine cancer cells is likewise less viable when exposed to SJG-136 (SG2000); GI50 values range from 0.33 to >100 nM after an hour of treatment and from <0.03 to 17.33 nM when exposed continuously [2].
ln Vivo	SJG-136-induced H2AX phosphorylation shows good correspondence but is less sensitive than focal measurements. SJG-136 at 0.30 mg/kg had a more potent antitumor effect on CMeC-1 tumors than SJG-136 at 0.15 mg/kg, either as a single dose or once weekly, administered by intravenous injection, for three weeks [2].
References	[1]. Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity. J Med Chem. 2001 Mar 1;44(5):737-48. [2]. Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours. BMC Vet Res. 2015 Aug 19;11:215.
Additional Infomation	SJG-136 has been used in trials studying the treatment of Recurrent Fallopian Tube Cancer, Secondary Acute Myeloid Leukemia, de Novo Myelodysplastic Syndromes, Recurrent Ovarian Epithelial Cancer, and Secondary Myelodysplastic Syndromes, among others. DNA Minor Groove Binding Agent SG2000 is a sequence-selective pyrrolobenzodiazepine (PBD) dimer with potential antineoplastic activity. Following intravenous administration, DNA minor groove binding agent SG2000 preferentially and covalently binds to purine-GATC-pyrimidine sequences, with the imine/carbinolamine moieties of SG2000 binding to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links and inhibits both DNA replication and gene transcription, which lead to the inhibition of cell growth. With a preference for binding to purine-GATC-pyrimidine sequences, SG2000 adducts do not appear to be susceptible to p53-mediated DNA excision repair.

Solubility Data

Solubility (In Vitro)

DMSO : ~33.33 mg/mL (~59.88 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.49 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 25.0 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. Solubility in Formulation 2: 2.08 mg/mL (3.74 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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 3: ≥ 2.08 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7966 mL	8.9830 mL	17.9659 mL
	5 mM	0.3593 mL	1.7966 mL	3.5932 mL
	10 mM	0.1797 mL	0.8983 mL	1.7966 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.