Raludotatug Deruxtecan  (Synonyms: R-DXd; DS-6000)

Raludotatug Deruxtecan is an antibody-drug conjugate targeting CDH6, with an EC₅₀ of 64.7 ng/mL in humans, 70.4 ng/mL in cynomolgus monkeys, and 228 ng/mL in mice. Raludotatug Deruxtecan specifically binds to CDH6 on the surface of cancer cells, triggers lysosomal internalization, and releases the DXd payload that inhibits TOP1. Raludotatug Deruxtecan induces DNA damage, Chk1 phosphorylation, caspase-3 cleavage, apoptosis, and bystander cell death. Raludotatug Deruxtecan is applicable to research related to serous ovarian cancer and renal cell carcinoma^[1].

Raludotatug deruxtecan (R-DXd) (0.001-1000 ng/mL; 6 days) exerts CDH6-dependent cell growth-inhibitory activity, potently inhibiting growth of CDH6-positive NIH:OVCAR-3 and PA-1 ovarian cancer cells, while having no effect on CDH6-negative ES-2 ovarian cancer cells^[1].
Raludotatug deruxtecan (R-DXd) (0.001-1000 ng/mL; 6 days) exerts CDH6-dependent cell growth-inhibitory activity, as its cytotoxic effect is abrogated in CDH6-knockout NIH:OVCAR-3 cells despite preserved sensitivity to free DXd^[1].
Raludotatug deruxtecan (R-DXd) (10 ng/mL; 6, 8, or 10 days) exhibits a bystander antitumor effect, where payload released from CDH6-positive cells diffuses to kill adjacent CDH6-negative cells^[1].
Raludotatug deruxtecan (R-DXd) (3 μg/mL; 3 days) induces DNA damage and apoptosis in CDH6-positive PA-1 ovarian cancer cells^[1].
Raludotatug deruxtecan (R-DXd) (10 nmol/L; 0, 0.5, 1, 3, 6, 12, 24, or 48 hours at 37°C) exhibits high internalization efficiency in CDH6-positive NIH:OVCAR-3 ovarian cancer cells, with nearly complete internalization within 24 hours^[1].
Raludotatug deruxtecan (R-DXd) (10 nmol/L; 0, 0.5, 1, 3, 6, 12, 24, or 48 hours at 37°C) reduces cell-surface CDH6 expression in CDH6-positive NIH:OVCAR-3 ovarian cancer cells, but CDH6 expression recovers rapidly if unbound R-DXd is removed from the medium^[1].
Raludotatug deruxtecan (R-DXd) (10 μg/mL; up to 24 hours at 37°C) binds to CDH6 at cell-cell boundaries, is internalized, and traffics to lysosomes in CDH6-expressing CHO-K1 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Raludotatug Deruxtecan (10 mg/kg; i.v.; single dose) induces tumor regression in carboplatin- and paclitaxel-refractory ovarian cancer xenografts without serious body weight loss^[1].
Raludotatug Deruxtecan (10 mg/kg; i.v.; days 0 and 21) induces significant tumor regression in CDH6-positive ovarian and renal cell carcinoma patient-derived xenograft models, but not in CDH6-negative models^[1].
Raludotatug Deruxtecan (3 mg/kg; i.v.; single dose on day 0 for PA-1 models; 10 mg/kg; i.v.; single dose on day 0 for JHOC-5 models) exhibits equivalent antitumor efficacy in parental and sCDH6-overexpressing ovarian cancer xenografts, indicating sCDH6 does not inhibit its activity^[1].
Raludotatug Deruxtecan (10-80 mg/kg; i.v.; once every 3 weeks for 6 weeks for 10, 30 mg/kg; single dose for 80 mg/kg) has a highest non-severely toxic dose of 30 mg/kg in cynomolgus monkeys, with mild-to-moderate, mostly reversible toxicity observed at this dose^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

2610074-57-0

Liquid

Colorless to light yellow

[Raludotatug Deruxtecan]

Shipping with dry ice.

-80°C, protect from light

• [1]. Suzuki H, et al. Raludotatug Deruxtecan, a CDH6-Targeting Antibody-Drug Conjugate with a DNA Topoisomerase I Inhibitor DXd, Is Efficacious in Human Ovarian and Kidney Cancer Models. Mol Cancer Ther. 2024;23(3):257-271.  [Content Brief]