171335-80-1

Basic information

• Product Name: Exatecan
• Synonyms: 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)-, MONOMETHANESULFONATE (SALT);exatecan alideximer;(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;DX 8951
• CAS NO: 171335-80-1
• Molecular Formula: C₂₄H₂₂FN₃O₄
• Molecular Weight: 435.45
• Mol File: 171335-80-1.mol

Chemical Properties

• Boiling Point: 818.4 °C at 760 mmHg
• Flash Point: 448.7 °C
• Appearance: /
• Density: 1.53 g/cm³
• Vapor Pressure: 2.47E-28mmHg at 25°C
• Refractive Index: 1.734
• PKA: 11.19±0.40(Predicted)
• CAS DataBase Reference: Exatecan(CAS DataBase Reference)
• NIST Chemistry Reference: Exatecan(171335-80-1)
• EPA Substance Registry System: Exatecan(171335-80-1)

Safety Data

• Hazardous Substances Data: 171335-80-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Exatecan is used as a cytotoxic agent for its ability to inhibit DNA topoisomerase I, which is essential for various cellular processes such as DNA replication, transcription, and recombination. This inhibition leads to the prevention of cancer cell proliferation and the induction of cell death, making it a promising candidate for the development of targeted cancer therapies.
Used in Antibody-Drug Conjugate (ADC) Research:
Exatecan is used as a potent payload in the development of antibody-drug conjugates (ADCs). These are a type of targeted cancer therapy that combines the specificity of monoclonal antibodies with the cytotoxic properties of chemotherapy drugs. By attaching Exatecan to an antibody that selectively binds to cancer cells, the conjugate can deliver the toxic payload directly to the tumor, minimizing damage to healthy cells and potentially improving treatment outcomes.
Used in Cancer Treatment:
Exatecan is used as a chemotherapeutic agent for the treatment of various types of cancer. Its mechanism of action involves inhibiting DNA topoisomerase I, which disrupts the cancer cell's ability to replicate and transcribe DNA, ultimately leading to cell death. This targeted approach may offer a more effective and less toxic alternative to traditional chemotherapy for certain cancer types.

Biological Activity

Exatecan (DX-8951) is a DNA topoisomerase I (topoisomerase I) inhibitor with IC50 of 2.2 μM (0.975 μg/mL) for cancer research.

in vitro

Exatecan is a potent topoisomerase I inhibitor, with an IC 50 of 0.975 μg/mL. Exatecan Mesylate (DX-8951f) significantly inhibits the proliferation of several cancer cell lines, with mean GI 50 s of 2.02 ng/mL, 2.92 ng/mL, 1.53 ng/mL, and 0.877 ng/mL for breast cancer cells, colon cancer cells, stomach cancer cells and lung cancer cells, respectively. Exatecan Mesylate (DX-8951f) displays cytotoxic activities against PC-6, PC-6/SN2-5 cells, with mean GI 50 s of 0.186 and 0.395 ng/mL, respctively. Exatecan Mesylate (34 nM) stabilizes DNA-TopoI complexes in PC-6 and PC-6/SN2-5 cells.

in vivo

Exatecan Mesylate (DX-8951f, 3.325-50 mg/kg, i.v.) exhibits antitumor activities in the mice model bearing tumor cells, without toxic death. Exatecan Mesylate (15, 25 mg/kg, i.v.) hightly inhibits MIA-PaCa, BxPC-3 primary tumor growth in the MIA-PaCa-2 early-stage model and early-stage model of BxPC-3. Exatecan Mesylate (15, 25 mg/kg, i.v.) also significantly suppresses BxPC-3 lymphatic metastasis and completely eliminates lung metastasis in the BxPC-3 late-stage cancer model.

InChI:InChI=1/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

Synthetic route

(18S,59S)-18-((benzyloxy)carbonyl)-59-((S)-2-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanamido)propanamido)-3,16,21,37,53,60,63,66,69-nonaoxo-1-phenyl-2,25,28,31,34,41,44,47,50-nonaoxa-17,22,38,54,61,64,67,70-octaazadoheptacontan-72-oic acid + exatecan (171335-80-1) → C90H131FN14O29

Conditions

Yield

Stage #1: (18S,59S)-18-((benzyloxy)carbonyl)-59-((S)-2-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanamido)propanamido)-3,16,21,37,53,60,63,66,69-nonaoxo-1-phenyl-2,25,28,31,34,41,44,47,50-nonaoxa-17,22,38,54,61,64,67,70-octaazadoheptacontan-72-oic acid; exatecan With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide at 20℃; for 6h; Stage #2: With trifluoroacetic acid In dichloromethane for 1h;

72%

1-hydroxy-cyclopentanecarboxylic acid (16841-19-3) + exatecan (171335-80-1) → C30H30FN3O6

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	32.6%

(R)-Mandelic Acid (611-71-2) + exatecan (171335-80-1) → C32H28FN3O6

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	23.3%

2-methyllactic acid (594-61-6) + exatecan (171335-80-1) → C28H28FN3O6

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	20.8%

D-Lactic acid (10326-41-7) + exatecan (171335-80-1) → C27H26FN3O6

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	20.6%

(2S)-2-hydroxybutanoic acid (3347-90-8) + exatecan (171335-80-1) → C28H28FN3O6

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃;	20.1%

(2R)-2-(3,5-difluorophenyl)-2-hydroxyacetic acid + exatecan (171335-80-1) → C32H26F3N3O6

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	19.4%

C31H40N6O10 + exatecan (171335-80-1) → C55H60FN9O13

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1.5h; Cooling with ice; Inert atmosphere;	17%

3,4-(methylenedioxy)mandelic acid (27738-46-1) + exatecan (171335-80-1) → C33H28FN3O8

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	11.7%

C37H54N6O14 + exatecan (171335-80-1) → C61H74FN9O17

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	80 mg

C39H49N9O12S + exatecan (171335-80-1) → C57H66FN11O13S

Conditions	Yield
With pyridine; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 24℃; for 48h;	123 mg

N-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-L-valyl-N5-carbamoyl-N[4-({[(4-nitrophenoxy)carbonyl]oxy}methyl)phenyl]-L-ornithinamide (159857-81-5) + exatecan (171335-80-1) → C53H60FN9O12

Conditions	Yield
With pyridine; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 24℃; for 48h;	139 mg