(11aS,11a'S)-configured PBD dimer (single defined stereoisomer); free base (no salt)
Bystander
Partial
PAMPA rank
-
MW
584.7 Da
XLogP3
2.8
logD₇.₄
2.5
TPSA
102 Ų
pKa
5 pKa
Charge pH 7.4
0
H-bond donors
0
H-bond acceptors
8
IC50 (HCEC)
-
Formula
C33H36N4O6
PubChem CID
90132565
ADCdb payload
PAY0LZRXU
Hydrophobicity · logD₇.₄
hydrophilic −2+2.5+4 lipophilic
Bioactivity note
SG3199 (free warhead) is a potent DNA minor-groove interstrand cross-linking PBD dimer with mean GI50 ~151.5 pM across a panel of human solid-tumor and hematological cell lines (Hartley et al., Sci Rep 2018). ADCdb reports clinical/efficacy data for the ADC: Phase 2 SCLC ORR 12.4
DLL3-targeted PBD-dimer ADC (SC16 humanized IgG1 + tesirine [SG3249] Val-Ala/PEG8 maleimide linker + SG3199 PBD dimer payload, DAR 2). Sponsor AbbVie (originally Stemcentrx, acquired 2016). Never approved; orphan-drug designation only; entire program discontinued 2019 after the Phase 3 TAHOE (2L) and MERU (maintenance) trials failed for efficacy/futility. ADCdb lists DRG0ULCEQ; aliases include Rova-T, SC16LD6.5, SC-0002. NOTE a DISTINCT program "SC-002" (ADCdb DRG0UUEEH; Mansfield Lung Cancer 2020) exists and should not be conflated with Rova-T. DOMINANT (non-ocular) TOXICITIES = serosal-effusion/capillary-leak/edema syndrome + photosensitivity, NOT classic ADC ocular toxicity: pleural effusion TRINITY 32% (G3+ 5%)/MERU 26.6%/TAHOE ~28.6%; pericardial effusion TRINITY 15% (G3+ 4%)/MERU 16.8%/TAHOE ~19.9%; peripheral edema TRINITY 31% (G3+ 2%)/MERU 25.8%; photosensitivity reaction TRINITY 36% (G3+ 7%)/MERU 24.7%/TAHOE 16%; thrombocytopenia TRINITY 22% (G3+ 11%). These respiratory/serosal/dermatologic/edema PTs fall outside the schema's organ_system enum so are recorded here rather than as toxicity_rows. OCULAR (priority): monotherapy ocular toxicity is essentially absent at RP2D — TRINITY (n=339) reported 0 ocular AEs and TAHOE (n=287) reported 0 eye disorders in the MedDRA SOC; MERU (n=368) reported ONLY 3 serious eye AEs (periorbital swelling 2/368=0.54%, angle-closure glaucoma 1/368=0.27%, eyelid oedema 1/368=0.27%), most likely adnexal manifestations of the systemic edema syndrome rather than ocular-surface toxicity; Phase 1 (Rudin 2017) reported a single Grade 3 photophobia (1/74 SCLC). NO keratopathy/corneal or conjunctival signal in any monotherapy trial. The only meaningful ocular signal is in the COMBINATION trial NCT03026166 (Rova-T 0.3 mg/kg Q6W + nivolumab ± ipilimumab): vision blurred 3.3% (1/30 doublet) to 8.3% (1/12 triplet), and in the 12-patient triplet arm dry eye, cataract, retinopathy, xerophthalmia, eyelid oedema, periorbital oedema, ocular hyperaemia, eye pruritus and visual impairment each 8.3% (1/12) — all non-serious and heavily CONFOUNDED by checkpoint-inhibitor immune-related ocular AEs, so not cleanly attributable to Rova-T. ae_corneal/conjunctival/dry-eye/blurred-vision left blank for the ocular group because monotherapy reported none and sub-threshold (<5% non-serious) PTs are not tabulated. CTCAE v4.03 (confirmed Rudin 2017 & TRINITY). Linker physchem (LIN0YRUBS) identical to Loncastuximab tesirine (shared tesirine linker); SG3199 payload physchem are standard shared PBD-dimer values. No peripheral neuropathy reported (expected for a DNA-crosslinker PBD payload).