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PBD dimer - CAS 1222490-34-7 Catalog number: BADC-00340
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PBD dimer is a cytotoxic agent, used as the cytotoxic component in antibody-drug conjugates.
Category
ADCs Cytotoxin
Product Name
PBD dimer
CAS
1222490-34-7
Catalog Number
BADC-00340
Molecular Formula
C42H39N5O7
Molecular Weight
725.79
Target
Ordering Information
| Catalog Number | Size | Price | Quantity |
|---|---|---|---|
| BADC-00340 | 1 mg | $899 |
Description
PBD dimer is a cytotoxic agent, used as the cytotoxic component in antibody-drug conjugates.
Synonyms
8-(3-((2-(4-Aminophenyl)-7-methoxy-5-oxo-1,11abeta-dihydro-5H-pyrrolo(2,1-C)(1,4)benzodiazepine-8-yl)oxy)propoxy)-7-methoxy-2-(4-methoxyphenyl)-1,11abeta-dihydro-5H-pyrrolo(2,1-C)(1,4)benzodiazepine-5-one;
IUPAC Name
(6aS)-3-[3-[[(6aS)-2-methoxy-8-(4-methoxyphenyl)-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-8-(4-aminophenyl)-2-methoxy-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-11-one
Canonical SMILES
COc1ccc(cc1)C2=CN3[C@@H](C2)C=Nc4cc(OCCCOc5cc6N=C[C@@H]7CC(=CN7C(=O)c6cc5OC)c8ccc(N)cc8)c(OC)cc4C3=O
InChI
InChI=1S/C42H39N5O7/c1-50-32-11-7-26(8-12-32)28-16-31-22-45-36-20-40(38(52-3)18-34(36)42(49)47(31)24-28)54-14-4-13-53-39-19-35-33(17-37(39)51-2)41(48)46-23-27(15-30(46)21-44-35)25-5-9-29(43)10-6-25/h5-12,17-24,30-31H,4,13-16,43H2,1-3H3/t30-,31-/m0/s1
InChIKey
OMRPLUKQNWNZAV-CONSDPRKSA-N
Density
1.4±0.1 g/cm3
Flash Point
545.1±34.3 °C
Index Of Refraction
1.676
LogP
2.87
Vapour Pressure
0.0±0.3 mmHg at 25°C
In Vitro
The PBD dimer binds only moderately to proteins (65-75%), and in vitro cytotoxicity studies confirmed IC(50) values of 4-30 nM with a panel of human cell lines.
In Vivo
Antibody-drug conjugates (ADC) containing pyrrolobenzodiazepine (PBD) dimers are being evaluated clinically in both hematologic and solid tumors. These include ADCT-301 (camidanlumab tesirine) and ADCT-402 (loncastuximab tesirine) in pivotal phase II trials that contain the payload tesirine, which releases the PBD dimer warhead SG3199. An important consideration in future clinical development is acquired resistance. The aim was to generate and characterize PBD acquired resistant cell lines in both hematologic and solid tumor settings. Human Karpas-299 (ALCL) and NCI-N87 (gastric cancer) cells were incubated with increasing IC50 doses of ADC (targeting CD25 and HER2, respectively) or SG3199 in a pulsed manner until stable acquired resistance was established. The level of resistance achieved was approximately 3,000-fold for ADCT-301 and 3-fold for SG3199 in Karpas-299, and 8-fold for ADCT-502 and 4-fold for SG3199 in NCI-N87. Cross-resistance between ADC and SG3199, and with an alternative PBD-containing ADC or PBD dimer was observed. The acquired resistant lines produced fewer DNA interstrand cross-links, indicating an upstream mechanism of resistance. Loss of antibody binding or internalization was not observed. A human drug transporter PCR Array revealed several genes upregulated in all the resistant cell lines, including ABCG2 and ABCC2, but not ABCB1(MDR1).
Appearance
Soild powder
Purity
≥95%
Shipping
Room temperature
Boiling Point
977.7±65.0 °C at 760 mmHg
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