Drug Information

General Information of This Drug
Drug ID DRG00018
Drug Name 7-Ethyl-10-hydroxycamptothecin
Synonyms
7-Ethyl-10-hydroxycamptothecin; 86639-52-3; SN-38; SN 38 lactone; SN 38; 7-Ethyl-10-hydroxy-camptothecin; (S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 10-Hydroxy-7-ethylcamptothecin; SN38; 7-Ethyl-10-hydroxy-20(S)-camptothecin; NK 012; NK-012; NK012; CHEBI:8988; 113015-38-6; IT-141; NSC673596; 0H43101T0J; (19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione; (4S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; CAMPTOTHECIN, 7-ETHYL-10-HYDROXY-; (4S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione; 7-ethyl-10-hydroxy-20(s)-campthothecin; LE-SN38; Captothecin, 7-ethyl-10-hydroxy-; MFCD00871873; UNII-0H43101T0J; C22H20N2O5; 110714-48-2; 1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE, 4,11-DIETHYL-4,9-DIHYDROXY-, (4S)-; 1H-Pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, 4,11-diethyl-4,9-dihydroxy-, (4S)-; AvaChem1025; (+)-7-ETHYL-10-HYDROXYCAMPTOTHECIN; diethyl(dihydroxy)[?]dione; SN 38- Bio-X; SCHEMBL34018; GTPL6925; SN 38 [WHO-DD]; DTXSID4040399; 10-hydroxy-7-ethyl camptothecin; 10-hydroxy-7-ethyl-camptothecin; EX-A989; HMS3413B12; HMS3652P12; HMS3677B12; BCP01386; 7-Ethyl-10-hydroxy-20(S)-CPT; BDBM50418088; s4908; AKOS015920433; AC-1357; BCP9000200; CCG-264764; CS-1579; DB05482; NSC-673596; SN-38(NK-012)?; NCGC00167831-01; NCGC00167831-05; AS-13533; BE164132; BP-24513; HY-13704; NCI60_026056; 7-Ethyl-10-hydroxy-20-(S)-camptothecine; E0748; FT-0630943; FT-0674607; FT-0674608; NS00069821; SW219948-1; S-(+)-7-ETHYL-10-HYDROXYCAMPOTHECIN; EN300-122379; NK012 , SN 38; A857464; Q-100871; Q1750127; 7-Ethyl-10-hydroxycamptothecin, >=98% (HPLC), powder; Z1541759909; (19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione; (19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione; (4S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)dione, AldrichCPR; (4S)-4,9-Dihydroxy-4,11-diethyl-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione;SN-38; (S)-4,11-Diethyl-4,9-di-OH-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione; 1H-Pyrano[3',7]indolizino[1,2-b]quinoline- 3,14(4H,12H)-dione, 4,11-diethyl-4,9-dihydroxy-, (4S)-; 7-Ethyl-10-hydroxycamptothecin ((S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione); H-Pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione, 4,11-diethyl-4,9-dihydroxy-, (S)-; RS4
   Click to Show/Hide
Target(s) DNA topoisomerase 1 (TOP1)  Target Info 
Structure
Formula
C22H20N2O5
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 392.4
Lipid-water partition coefficient (xlogp) 1.4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
Rotatable Bond Count (rotbonds) 2
PubChem CID
104842
Canonical smiles
CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)C4(CC)O)C2=NC5=C1C=C(C=C5)O
InChI
InChI=1S/C22H20N2O5/c1-3-12-13-7-11(25)5-6-17(13)23-19-14(12)9-24-18(19)8-16-15(20(24)26)10-29-21(27)22(16,28)4-2/h5-8,25,28H,3-4,9-10H2,1-2H3/t22-/m0/s1
InChIKey
FJHBVJOVLFPMQE-QFIPXVFZSA-N
IUPAC Name
(19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
The activity data of This Drug
Standard Type Value Administration times Cell line Cell line ID Ref.
Half Maximal Inhibitory Concentration (IC50) 26.41 nM 72 h U-87MG cell CVCL_0022 [1]
Half Maximal Growth Inhibition (GI50) 3 nM N.A. MCF-7 cell CVCL_0031 [2]
Half Maximal Growth Inhibition (GI50) 23 nM N.A. HCT 116 cell CVCL_0291 [2]
Half Maximal Growth Inhibition (GI50) 110 nM N.A. MKN-28 cell CVCL_1416 [2]
Half Maximal Inhibitory Concentration (IC50) 0.43 nM N.A. PC-6 cell CVCL_C002 [3]
Half Maximal Inhibitory Concentration (IC50) 0.55 nM N.A. HCT 116 cell CVCL_0291 [3]
Half Maximal Inhibitory Concentration (IC50) 0.78 nM N.A. HCT 116 cell CVCL_0291 [4]
Half Maximal Inhibitory Concentration (IC50) 2.8 nM N.A. QG-56 cell CVCL_6943 [3]
Half Maximal Inhibitory Concentration (IC50) 3.3 nM N.A. NCI-H460 cell CVCL_0459 [3]
Half Maximal Inhibitory Concentration (IC50) 4 nM N.A. DU145 cell CVCL_0105 [5]
Half Maximal Inhibitory Concentration (IC50) 5.9 nM N.A. HT29 cell CVCL_A8EZ [6]
Half Maximal Inhibitory Concentration (IC50) 6 nM N.A. NCI-H128 cell CVCL_1460 [7]
Half Maximal Inhibitory Concentration (IC50) 8 nM N.A. Capan-1 cell CVCL_0237 [8]
Half Maximal Inhibitory Concentration (IC50) 8 nM N.A. MKN45 cell CVCL_0434 [7]
Half Maximal Inhibitory Concentration (IC50) 8.9 nM N.A. L1210 cell CVCL_0382 [9]
Half Maximal Inhibitory Concentration (IC50) 11 nM N.A. A-549 cell CVCL_0023 [8]
Half Maximal Inhibitory Concentration (IC50) 16 nM N.A. A-549 cell CVCL_0023 [7]
Half Maximal Inhibitory Concentration (IC50) 18 nM N.A. A-549 cell CVCL_0023 [10]
Half Maximal Inhibitory Concentration (IC50) 28 nM N.A. A-549 cell CVCL_0023 [11]
Half Maximal Inhibitory Concentration (IC50) 35.3 nM N.A. PC-3 cell CVCL_0035 [12]
Half Maximal Inhibitory Concentration (IC50) 54 nM N.A. HT29 cell CVCL_A8EZ [13]
Half Maximal Inhibitory Concentration (IC50) 88 nM N.A. A-549 cell CVCL_0023 [14]
Half Maximal Inhibitory Concentration (IC50) 220 nM N.A. NCI-H460 cell CVCL_0459 [15]
Half Maximal Inhibitory Concentration (IC50) 300 nM N.A. A-549 cell CVCL_0023 [16]
Half Maximal Inhibitory Concentration (IC50) 300 nM N.A. HeLa cell CVCL_0030 [16]
Half Maximal Inhibitory Concentration (IC50) 370 nM N.A. MCF-7 cell CVCL_0031 [17]
Half Maximal Inhibitory Concentration (IC50) 480 nM N.A. SK-MEL-24 cell CVCL_0599 [18]
Half Maximal Inhibitory Concentration (IC50) 4.98 uM N.A. CCD-841CoN cell CVCL_2871 [11]
Each Peptide-drug Conjugate Related to This Drug
Full Information of The Activity Data of The PDC(s) Related to This Drug
SN38-HKD [Investigative]
 PDC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [19]
Indication Triple-negative breast cancer
Efficacy Data Tumor Growth Inhibition value (TGI) 43% (Day 14)
Evaluation Method Tumor volume detection assay
Administration Time 4-injection regimen (on day 0, 2, 4, and 6)
Administration Dosage 10 mg/kg
MOA of PDC
N38-HKD increases infiltration, activity, and viability of CD8+T cells, and thus inhibits the growth of primary tumors and pulmonary metastasis. This study highlights the synergistic modulation of cancerous cells and TECs with integrin-targeting PDC filaments as a promising strategy for TNBC chemoimmunotherapy.
Description
SN38-HKD/RGDR slowed the 4T1 tumor growth by 74%, while irinotecan and SN38-HKD only showed 28% and 43% tumor growth inhibition, respectively, which was further confirmed by its capability in reducing tumor burden.
In Vivo Model 4T1 tumor-bearing mice.
In Vitro Model Mammary carcinoma 4T1 cell CVCL_0125
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [19]
Indication Triple-negative breast cancer
Efficacy Data Tumor Growth Inhibition value (TGI) 40% (Day 18)
Evaluation Method Tumor volume detection assay
Administration Time 4-injection regimen (on day 0, 2, 4, and 6)
Administration Dosage 10 mg/kg
MOA of PDC
N38-HKD increases infiltration, activity, and viability of CD8+T cells, and thus inhibits the growth of primary tumors and pulmonary metastasis. This study highlights the synergistic modulation of cancerous cells and TECs with integrin-targeting PDC filaments as a promising strategy for TNBC chemoimmunotherapy.
Description
SN38-HKD/RGDR slowed the 4T1 tumor growth by 74%, while irinotecan and SN38-HKD only showed 28% and 43% tumor growth inhibition, respectively, which was further confirmed by its capability in reducing tumor burden.
In Vivo Model EMT6 tumor-bearing mice.
In Vitro Model Mammary gland malignant neoplasms EMT6 cell CVCL_1923
SN38-HKD/RGDR [Investigative]
 PDC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [19]
Indication Triple-negative breast cancer
Efficacy Data Tumor Growth Inhibition value (TGI) 74% (Day 14)
Evaluation Method Tumor volume detection assay
Administration Time 4-injection regimen (on day 0, 2, 4, and 6)
Administration Dosage 10 mg/kg
MOA of PDC
N38-HKD/RGDR increases infiltration, activity, and viability of CD8+ T cells, and thus inhibits the growth of primary tumors and pulmonary metastasis. This study highlights the synergistic modulation of cancerous cells and TECs with integrin-targeting PDC filaments as a promising strategy for TNBC chemoimmunotherapy.
Description
SN38-HKD/RGDR slowed the 4T1 tumor growth by 74%, while irinotecan and SN38-HKD only showed 28% and 43% tumor growth inhibition, respectively, which was further confirmed by its capability in reducing tumor burden.
In Vivo Model 4T1 tumor-bearing mice.
In Vitro Model Mammary carcinoma 4T1 cell CVCL_0125
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [19]
Indication Triple-negative breast cancer
Efficacy Data Tumor Growth Inhibition value (TGI) 75% (Day 18)
Evaluation Method Tumor volume detection assay
Administration Time 4-injection regimen (on day 0, 2, 4, and 6)
Administration Dosage 10 mg/kg
MOA of PDC
N38-HKD/RGDR increases infiltration, activity, and viability of CD8+T cells, and thus inhibits the growth of primary tumors and pulmonary metastasis. This study highlights the synergistic modulation of cancerous cells and TECs with integrin-targeting PDC filaments as a promising strategy for TNBC chemoimmunotherapy.
Description
SN38-HKD/RGDR slowed the 4T1 tumor growth by 74%, while irinotecan and SN38-HKD only showed 28% and 43% tumor growth inhibition, respectively, which was further confirmed by its capability in reducing tumor burden.
In Vivo Model EMT6 tumor-bearing mice.
In Vitro Model Mammary gland malignant neoplasms EMT6 cell CVCL_1923
Cot-APTEDB-SN38 [Investigative]
 PDC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [20]
Indication Tumor
Efficacy Data Anti-tumor activity 23.90%
Administration Time 6 days
Administration Dosage Equivalent to 2 mg SN38/kg
Description
In situ HC[cot-APTEDB-SN38/Abcot] at an SN38/kg dose-equivalent of 2 mg effectively suppressed tumor growth and showed much greater antitumor activity (49.8% inhibition) than both cot-APTEDB-SN38 alone (23.9% inhibition) and CPT-11 (10.6% inhibition).
In Vivo Model EDB-positive human glioblastoma-bearing mice.
Half life period 2.01 h
T7-SN-38 [Investigative]
 PDC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Glioblastoma
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 70.07nM
Evaluation Method XTT assay
Administration Time 72 h
MOA of PDC
In the present work, the cytotoxic drug SN-38 is coupled to the tumor-targeting T7 peptide via a cathepsin B cleavable VA peptide linker. This ensures that the drug remains covalently bound until it reaches the intended site of action, where Cat B is overexpressed to release the drug. Within this framework, our research pursuits entail the synthesis and characterization of a T7-SN-38-targeted drug conjugate using strain-promoted azide-alkyne cycloaddition (SPAAC). Our investigation extended to evaluating the cellular uptake and assessing the cytotoxicity of the drug conjugate in U87MG glioblastoma cells.

   Click to Show/Hide
Description
Further, IC50values of SN-38 and T7-SN-38 on U87MG cells at 72 h were determined. An estimated IC50value of 26.41nM was obtained for SN-38, which was considerably lower than an IC50value of 70.07nM obtained for the T7-SN-38 conjugate. These IC50data confirm the greater cytotoxicity of the pure drug compared to the conjugate at 72 h (p< 0.05).
In Vitro Model Glioblastoma U-87MG cell CVCL_0022
References
Ref 1 Development of a Targeted SN-38-Conjugate for the Treatment of Glioblastoma. ACS Omega. 2024 Jan 4;9(2):2615-2628. doi: 10.1021/acsomega.3c07486. eCollection 2024 Jan 16.
Ref 2 Lamellarin-inspired potent topoisomerase I inhibitors with the unprecedented benzo[g][1]benzopyrano[4,3-b]indol-6(13H)-one scaffold. Bioorg Med Chem. 2019 Jan 15;27(2):265-277. doi: 10.1016/j.bmc.2018.11.037. Epub 2018 Nov 28.
Ref 3 Synthesis of new camptothecin analogs with improved antitumor activities. Bioorg Med Chem Lett. 2009 Apr 1;19(7):2018-21. doi: 10.1016/j.bmcl.2009.02.031. Epub 2009 Feb 12.
Ref 4 A series of camptothecin prodrugs exhibit HDAC inhibition activity. Bioorg Med Chem. 2018 Sep 1;26(16):4706-4715. doi: 10.1016/j.bmc.2018.08.008. Epub 2018 Aug 4.
Ref 5 Synthesis and bioevaluation of 22-hydroxyacuminatine analogs. Bioorg Med Chem Lett. 2008 Mar 15;18(6):2143-6. doi: 10.1016/j.bmcl.2008.01.082. Epub 2008 Jan 30.
Ref 6 Semisynthesis of triptolide analogues: effect of -lactone and C-14 substituents on cytotoxic activities. Bioorg Med Chem Lett. 2011 May 15;21(10):3046-9. doi: 10.1016/j.bmcl.2011.03.025. Epub 2011 Mar 16.
Ref 7 Synthesis and biological evaluation of novel A-ring modified hexacyclic camptothecin analogues. J Med Chem. 2001 May 10;44(10):1594-602. doi: 10.1021/jm0004751.
Ref 8 Design, Synthesis, and Biological Evaluation of HSP90 Inhibitor-SN38 Conjugates for Targeted Drug Accumulation. J Med Chem. 2020 May 28;63(10):5421-5441. doi: 10.1021/acs.jmedchem.0c00305. Epub 2020 May 11.
Ref 9 Synthesis of water-soluble (aminoalkyl)camptothecin analogues: inhibition of topoisomerase I and antitumor activity. J Med Chem. 1991 Jan;34(1):98-107. doi: 10.1021/jm00105a017.
Ref 10 F10, a new camptothecin derivative, was identified as a new orally-bioavailable, potent antitumor agent. Eur J Med Chem. 2020 Sep 15;202:112528. doi: 10.1016/j.ejmech.2020.112528. Epub 2020 Jul 5.
Ref 11 New camptothecin derivatives for generalized oncological chemotherapy: Synthesis, stereochemistry and biology. Bioorg Med Chem Lett. 2021 Aug 15;46:128146. doi: 10.1016/j.bmcl.2021.128146. Epub 2021 May 25.
Ref 12 Camptothecin analogs with bulky, hydrophobic substituents at the 7-position via a Grignard reaction. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5377-81. doi: 10.1016/j.bmcl.2004.08.010.
Ref 13 10-Boronic acid substituted camptothecin as prodrug of SN-38. Eur J Med Chem. 2016 Jun 30;116:84-89. doi: 10.1016/j.ejmech.2016.03.063. Epub 2016 Mar 24.
Ref 14 7-Cycloalkylcamptothecin derivatives: Preparation and biological evaluation. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4107-9. doi: 10.1016/j.bmcl.2009.06.010. Epub 2009 Jun 6.
Ref 15 Synthesis and cytotoxic activity of new 9-substituted camptothecins. Bioorg Med Chem Lett. 2008 May 1;18(9):2781-7. doi: 10.1016/j.bmcl.2008.04.016. Epub 2008 Apr 10.
Ref 16 Folate Receptor Targeting and Cathepsin B-Sensitive Drug Delivery System for Selective Cancer Cell Death and Imaging. ACS Med Chem Lett. 2020 May 18;11(8):1514-1520. doi: 10.1021/acsmedchemlett.0c00031. eCollection 2020 Aug 13.
Ref 17 BN 80927: a novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II. Bioorg Med Chem Lett. 1999 Sep 6;9(17):2599-602. doi: 10.1016/s0960-894x(99)00428-x.
Ref 18 Artemisinin Derivatives with Antimelanoma Activity Show Inhibitory Effect against Human DNA Topoisomerase 1. ACS Med Chem Lett. 2020 Apr 10;11(5):1035-1040. doi: 10.1021/acsmedchemlett.0c00131. eCollection 2020 May 14.
Ref 19 Inhibiting Endothelial Cell-Mediated T Lymphocyte Apoptosis with Integrin-Targeting Peptide-Drug Conjugate Filaments for Chemoimmunotherapy of Triple-Negative Breast Cancer. Adv Mater. 2024 Jan;36(3):e2306676. doi: 10.1002/adma.202306676. Epub 2023 Nov 30.
Ref 20 Antibody-Assisted Delivery of a Peptide-Drug Conjugate for Targeted Cancer Therapy. Mol Pharm. 2019 Jan 7;16(1):165-172. doi: 10.1021/acs.molpharmaceut.8b00924. Epub 2018 Dec 17.