DAR0-8 mixture, average 3.53 +/- 0.05 by intact MS
%HMW aggregate
1.64 %
Formula
C16H18N2O6
Linker MW
334.328 Da
Linker TPSA
101.06 Ų
Linker xLogP
0.325
ADCdb linker
LIN0EBJON
In-vitro stability
-
Stability note
acAb t½ 3.94 d; SMCC is the highest intrinsic plasma stability among clinical linkers — non-cleavable thioether to charged Lys-MCC-DM1 catabolite (no bystander); deconjugation is not a significant pathway
Lys-MCC-DM1 (lysine-Nε-MCC-DM1; = Lys-SMCC-DM1 in literature), the principal charged catabolite; MCC-DM1 and free DM1 also detected at low levels in plasma
Mechanistic subtype
Tubulin-maytansinoid
Stereochem / salt
Free thiol maytansinoid; neutral
Bystander
No
PAMPA rank
5
MW
1103.7 Da
XLogP3
-0.2
logD₇.₄
-0.5
TPSA
312 Ų
pKa
2.2 pKa
Charge pH 7.4
Zwitterion
H-bond donors
5
H-bond acceptors
17
IC50 (HCEC)
-
Formula
C53H75ClN6O15S
PubChem CID
74832310
ADCdb payload
PAY0JCIBW
Potency IC50 (nM)
1
Hydrophobicity · logD₇.₄
hydrophilic −2-0.5+4 lipophilic
Bioactivity note
ADCdb lists T-DM1 cellular IC50 values spanning ~0.04 nM (high HER2-expressing lines) to >500 nM (low/negative HER2 lines), HER2-expression dependent. No isolated free-payload (DM1) IC50 is given on the ADCdb ADC page; DM1 is a potent antimitotic maytansinoid that inhibits tubuli
06
Dosing & regimen
Dosing
RP2D dose
3.6 mg/kg
Schedule
Q3W
Route
IV
Fractionated
No
n at RP2D
490
Dose basis
TBW
Trial phase
Approved
Dose-OAE available
No
Tox summary basis
RP2D
ADA rate (%)
5.3 %
07
Pharmacology
Clinical pharmacokinetics
By analyte · FDA label §12.3 + Drugs@FDA clinical-pharmacology reviews
Intact ADC
Total antibody
Free payload
Cmax
83.4ug/mL+1
86.3ug/mL
4.61ng/mL+1
AUC
489ug*day/mL
816ug*day/mL
9.11ng*day/mL
Tmax
end of infusionh
—
end of infusionh
t½
~4days
7.8days
—
CL
0.68L/day
5.4mL/day/kg
—
Vd
3.13L
45.2mL/kg
—
FDA label §12.3 Drugs@FDA reviewhover a value for dose / population / source · “+N” marks additional reported values
Per-cohort rates from the per-trial extraction, sorted by dose. Cross-trial comparison is subject to ascertainment / scale differences (see comparability above) — e.g. an early symptom-driven trial can read lower than a later systematic-exam trial at a higher dose.