Rovalpituzumab Tesirine

Synopsis, Chemistry

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Also known as: Rova-t, Rovalpituzumab-tesirin, Unii-p256hb60ff, Rovalpituzumab tesirine [inn], P256hb60ff, Rovalpituzumab tesirine [who-dd]

Molecular Formula

C₇₈H₁₀₈N₁₀O₂₅S

Molecular Weight

1617.8 g/mol

InChI Key

NQUUPTGRJYIXSL-YPDXTJLXSA-N

Rovalpituzumab Tesirine is an antibody-drug conjugate (ADC) containing a humanized IgG1 monoclonal antibody (MAb) directed against the delta-like protein 3 (DLL3), conjugated to the cytotoxic pyrrolobenzodiazepine (PBD) dimer D6.5 (SC-DR002) via a maleimide-containing linker with an eight-carbon polyethylene glycol spacer and a cathepsin B-cleavable valine-alanine dipeptide, with potential antineoplastic activity. The MAb moiety of rovalpituzumab tesirine selectively binds to DLL3 on tumor cell surfaces. Upon internalization of the ADC, the dipeptide linker is cleaved and D6.5 is released. Then the imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces DNA strand breaks, inhibits DNA replication, leads to G2/M cell cycle arrest, induces cell death, and inhibits the proliferation of DLL3-overexpressing tumor cells. DLL3, a membrane protein that binds to Notch receptors and regulates Notch-mediated signaling and gene transcription, is overexpressed by certain cancers but is rarely expressed by normal, healthy cells.

1 2D Structure

Rovalpituzumab Tesirine

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

(2R)-3-[(3R)-1-[3-[2-[2-[2-[2-[2-[2-[2-[2-[3-[[(2S)-1-[[(2S)-1-[4-[[(6S,6aS)-3-[5-[[(6aS)-2-methoxy-8-methyl-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]pentoxy]-6-hydroxy-2-methoxy-8-methyl-11-oxo-6a,7-dihydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl]oxymethyl]anilino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-3-oxopropyl]-2,5-dioxopyrrolidin-3-yl]sulfanyl-2-aminopropanoic acid

2.1.2 InChI

InChI=1S/C78H108N10O25S/c1-49(2)70(84-68(90)16-21-103-23-25-105-27-29-107-31-33-109-35-36-110-34-32-108-30-28-106-26-24-104-22-17-80-67(89)15-18-85-69(91)43-66(76(85)97)114-48-58(79)77(98)99)72(93)82-52(5)71(92)83-54-13-11-53(12-14-54)47-113-78(100)88-60-42-65(63(102-7)40-57(60)74(95)87-46-51(4)38-61(87)75(88)96)112-20-10-8-9-19-111-64-41-59-56(39-62(64)101-6)73(94)86-45-50(3)37-55(86)44-81-59/h11-14,39-42,44-46,49,52,55,58,61,66,70,75,96H,8-10,15-38,43,47-48,79H2,1-7H3,(H,80,89)(H,82,93)(H,83,92)(H,84,90)(H,98,99)/t52-,55-,58-,61-,66+,70-,75-/m0/s1

2.1.3 InChI Key

NQUUPTGRJYIXSL-YPDXTJLXSA-N

2.1.4 Canonical SMILES

CC1=CN2C(C1)C=NC3=CC(=C(C=C3C2=O)OC)OCCCCCOC4=C(C=C5C(=C4)N(C(C6CC(=CN6C5=O)C)O)C(=O)OCC7=CC=C(C=C7)NC(=O)C(C)NC(=O)C(C(C)C)NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCN8C(=O)CC(C8=O)SCC(C(=O)O)N)OC

2.1.5 Isomeric SMILES

CC1=CN2[C@@H](C1)C=NC3=CC(=C(C=C3C2=O)OC)OCCCCCOC4=C(C=C5C(=C4)N([C@H]([C@@H]6CC(=CN6C5=O)C)O)C(=O)OCC7=CC=C(C=C7)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCN8C(=O)C[C@H](C8=O)SC[C@@H](C(=O)O)N)OC

2.2 Synonyms

2.2.1 MeSH Synonyms

1. Sc16ld6.5

2. Sc-002

3. Sc002

2.2.2 Depositor-Supplied Synonyms

1. Rova-t

2. Rovalpituzumab-tesirin

3. Unii-p256hb60ff

4. Rovalpituzumab Tesirine [inn]

5. P256hb60ff

6. Rovalpituzumab Tesirine [who-dd]

7. Sc002

8. Rovalpituzumab Tesirine [usan:inn]

9. Sc0002

10. 1613313-09-9

2.3 Create Date

2018-01-14

3 Chemical and Physical Properties

Molecular Formula	C₇₈H₁₀₈N₁₀O₂₅S
Molecular Weight	1617.8 g/mol
XLogP3	-1.6
Hydrogen Bond Donor Count	7
Hydrogen Bond Acceptor Count	28
Rotatable Bond Count	53
Exact Mass	1616.72078014 g/mol
Monoisotopic Mass	1616.72078014 g/mol
Topological Polar Surface Area	456 Å²
Heavy Atom Count	114
Formal Charge	0
Complexity	3190
Isotope Atom Count	0
Defined Atom Stereocenter Count	7
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1