Payload Information

General Information of This Payload
Payload ID
PAY0LEIGJ
Name
Exatecan
Synonyms
Exatecan; 171335-80-1; Exatecan [INN]; Exatecan mesylate; DX-8951; DX-8951f; OC71PP0F89; (1S,9S)-1-Amino-9-ethyl-5-fluoro-1,2,3,9,12,15-hexahydro-9-hydroxy-4-methyl-10H,13H-benzo(de)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-10,13-dione; Dx 8951; UNII-OC71PP0F89; exatecan-mesylate; (1s,9s)-1-amino-9-ethyl-5-fluoro-1,2,3,9,12,15-hexahydro-9-hydroxy-4-methyl-10h,13h-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione; EXATECAN [MI]; EXATECAN [WHO-DD]; SCHEMBL2512959; CHEMBL1614650; DTXSID60169061; CHEBI:135709; EX-A2683; NSC829066; AKOS005146469; AT33978; BCP9000674; DB12185; NSC-829066; 10H,13H-Benzo(de)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-10,13-dione, 1-amino-9-ethyl-5-fluoro-1,2,3,9,12,15-hexahydro-9-hydroxy-4-methyl-, (1S,9S)-; 10H,13H-Benzo(de)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-10,13-dione, 1-amino-9-ethyl-5-fluoro-1,2,3,9,12,15-hexahydro-9-hydroxy-4-methyl-, (1S-trans)-; AC-32495; BP-27995; BP-27996; HY-13631; DB-064817; DX8951;DX 8951;DX-8951; J-521361; Q5419343; (10S,23S)-23-amino-10-ethyl-18-fluoro-10-hydroxy-19-methyl-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaene-5,9-dione; (1S,9S)-1-amino-9-ethyl-5-fluoro-9-hydroxy-4-methyl-2,3,12,15-tetrahydrobenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13(1H,9H)-dione
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Target(s) DNA topoisomerase 1 (TOP1)
 Target Info 
Structure
Formula
C24H22FN3O4
Isosmiles
CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C5[C@H](CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)N)O
PubChem CID
151115
InChI
InChI=1S/C24H22FN3O4/c1-3-24(31)14-6-18-21-12(8-28(18)22(29)13(14)9-32-23(24)30)19-16(26)5-4-11-10(2)15(25)7-17(27-21)20(11)19/h6-7,16,31H,3-5,8-9,26H2,1-2H3/t16-,24-/m0/s1
InChIKey
ZVYVPGLRVWUPMP-FYSMJZIKSA-N
IUPAC Name
(10S,23S)-23-amino-10-ethyl-18-fluoro-10-hydroxy-19-methyl-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaene-5,9-dione
Pharmaceutical Properties
Molecule Weight
435.4
Polar area
106
Complexity
950
xlogp Value
0.4
Heavy Count
32
Rot Bonds
1
Hbond acc
7
Hbond Donor
2
The activity data of This Payload
Standard Type Value Units Cell line Disease Model Cell line ID Reference
Half Maximal Inhibitory Concentration (IC50) 0.16 nM
MOLT-4 cells
Adult T acute lymphoblastic leukemia
CVCL_0013 
[1]
Half Maximal Inhibitory Concentration (IC50) 0.25 nM
CCRF-CEM cells
T acute lymphoblastic leukemia
CVCL_0207 
[1]
Half Maximal Inhibitory Concentration (IC50) 0.49 nM
DU145 cells
Prostate carcinoma
CVCL_0105 
[1]
Half Maximal Inhibitory Concentration (IC50) 0.58 nM
DMS 114 cells
Lung small cell carcinoma
CVCL_1174 
[1]
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
PRO-1184 [Phase 1/2]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Related Clinical Trial
NCT Number NCT05579366  Phase Status Phase 1/2
Clinical Description
Phase 1/2 study of PRO1184 in patients with locally advanced and/or metastatic solid tumors.
PRO-1160 [Phase 1/2]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Related Clinical Trial
NCT Number NCT05721222  Phase Status Phase 1/2
Clinical Description
Phase 1/2 study of PRO1160 in patients with renal cell carcinoma (RCC), nasopharyngeal carcinoma (NPC), or non-Hodgkin lymphoma (NHL).
CBX-12 [Phase 1/2]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 9.96% (Day 23)
Method Description
Ceralasertib=25 mg/kg.
In Vivo Model Colon cancer CDX model
In Vitro Model Colon cancer HCT 116 cells CVCL_0291
Experiment 2 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 42.76% (Day 35)
Method Description
Ceralasertib=25 mg/kg.
In Vivo Model Breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells CVCL_0062
Experiment 3 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 56.70% (Day 23)
Method Description
CBX-12=5 mg/kg.
In Vivo Model Colon cancer CDX model
In Vitro Model Colon cancer Colon cancer cells Homo sapiens
Experiment 4 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.32% (Day 35)
Method Description
CBX-12=10 mg/kg.
In Vivo Model Breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells CVCL_0062
Experiment 5 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 81.22% (Day 23)
Method Description
Ceralasertib=25 mg/kg + CBX-12=5 mg/kg.
In Vivo Model Colon cancer CDX model
In Vitro Model Colon cancer Colon cancer cells Homo sapiens
Experiment 6 Reporting the Activity Date of This ADC [1]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.40% (Day 35)
Method Description
Ceralasertib=25 mg/kg + CBX-12=10 mg/kg.
In Vivo Model Breast cancer CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells CVCL_0062
AMT-562 [Investigative]
 ADC Info 
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 71.80% (Day 28) Low HER3 expression (HER3+)
Method Description
AMT-562 (10 mg/kg, day 1) induces efficient tumor cell killing in cell line-derived models of Pancreatic cancer cell with HER3 expression with high expression.
In Vivo Model Pancreatic cancer PDX model (PDX: PDX-200930)
Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 40) Low HER3 expression (HER3+)
Method Description
AMT-562 (10 m ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of Pancreatic cancer cell with HER3 expression with high expression.
In Vivo Model Squamous cell carcinoma PDX model (PDX: PDX-361318)
Experiment 3 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 49) Low HER3 expression (HER3+)
Method Description
AMT-562 (10 m ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of Pancreatic cancer cell with HER3 expression with high expression.
In Vivo Model Pancreatic cancer PDX model (PDX: PDX-361319)
Trastuzumab-T1000-exatecan [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 59.00% (Day 27) Negative HER2 expression (HER2 -)
Method Description
T moiety (We conducted a four-week (day 1, 8, 15, 22, and 29) intermittent intravenous dose toxicity study of exatecan mesylate in rats (six animals/group) with a four-week recovery period (three of the six animals).
In Vivo Model MDA-MB-468 CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
References
Ref 1 TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor. Mol Cancer Ther. 2022 Jul 5;21(7):1090-1102.
Ref 2 Phase 1/2 Study of PRO1184 in Patients With Locally Advanced and/or Metastatic Solid Tumors, NCT05579366
Ref 3 Phase 1/2 Study of PRO1160 in Patients With Renal Cell Carcinoma (RCC), Nasopharyngeal Carcinoma (NPC), or Non-Hodgkin Lymphoma (NHL), NCT05721222
Ref 4 AMT-562, a novel HER3-targeting antibody drug conjugate, demonstrates a potential to broaden therapeutic opportunities for HER3-expressing tumors. Mol Cancer Ther. 2023 Jun 11:MCT-23-0198. doi: 10.1158/1535-7163.MCT-23-0198. Online ahead of print.
Ref 5 Antibody-Exatecan Conjugates with a Novel Self-immolative Moiety Overcome Resistance in Colon and Lung Cancer. Cancer Discov. 2023 Apr 3;13(4):950-973. doi: 10.1158/2159-8290.CD-22-1368.

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