Gemtuzumab ozogamicin

FDA-approved

Mylotarg; CMA-676

Target

CD33 · CD33

Sponsor

Wyeth/Pfizer

Indication

CD33+ AML

Target family

Siglec

RP2D dose

3 mg/m² (max 4.5 mg)

D1+D4+D7 inductionRP2D

Multi-organ toxicity

Fingerprint & organ drill-down

Also reported

0%severity100%

Assessed · clear

true 0%

No data

never assessed

0 adverse-event terms

Ocular

Any-grade

G3+

RP2D

sagittal schematic · Unknown

↳

Tissues shaded by reported adverse-event rate.

Cornea

Express.

0.07%

Limbus

Express.

0.03%

Conjunctiva

Express.

0.06%

Lens

Express.

Retina / RPE

Express.

0.46%

0.2 nTPM

Dominant tissue

Surface subtype

None

Reversibility

Unknown

Reported ocular events

No granular adverse-event rows recorded for this system.

Construct

Molecular anatomy

Antibody

IgG4

Humanized

Linker

Cleavable

2.5

DAR

Payload

Calicheamicin gamma1

DNA strand break

Linker structureC12H15NO3

CC(=O)c1ccc(OCCCC(N)=O)cc1

Payload structureC55H74IN3O21S4

CCN[C@H]1CO[C@H](C[C@@H]1OC)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2O[C@H]3C#C/C=C\\C#C[C@@]\\4(CC(=O)C(=C3/C4=C\\CSSSC)NC(=O)OC)O)C)NO[C@H]5C[C@@H]([C@@H]([C@H](O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)O[C@H]7[C@@H]([C@@H]([C@H]([C@@H](O7)C)O)OC)O)I)C)O)O

Antibody

Antibody & Fc engineering

Antibody

hP67.6

Isotype

IgG4

Origin

Humanized

Fc modifications

None

Glycoengineering

Standard

Effector silencing

None

FcγR binding

Retained

C1q binding

Reduced

Linker & conjugation

Linker chemistry

Linker profile

Linker

AcBut hydrazone + disulfide

Class

Cleavable

Cleavage

Cleavable

Attachment

Lysine

Conjugation

Conventional Lys (NHS)

Symmetry

Asymmetric

DAR (mean)

2.5

DAR homogeneity

Heterogeneous

Plasma t½

2.6 d

Cleavage trigger

pH/acid (hydrazone) + GSH/reductive (disulfide)

Release control

Conditional

Hydrophilicity mask

None

Formula

C12H15NO3

Linker MW

221.256 Da

Linker TPSA

69.39 Å²

Linker xLogP

1.5335

ADCdb linker

LIN0KWKDL

In-vitro stability

Stability note

Terminal t½ ~62 h after dose 1, ~90 h after dose 2 (9 mg/m² regimen); acid-labile hydrazone + disulfide intentionally plasma-labile, implicated in hepatotoxicity / VOD-SOS

Payload

Payload & physicochemistry

Payload profile

Payload

Calicheamicin gamma1

Class

Calicheamicin

Mechanism

DNA strand break

Released catabolite

N-acetyl-γ-calicheamicin (active calicheamicin derivative), released from the conjugated N-acetyl-γ-calicheamicin dimethylhydrazide (N-Ac-γ-cal-DMH) by nonenzymatic reduction of the disulfide bond

Mechanistic subtype

DNA-strand-break

Stereochem / salt

Bystander

Partial

PAMPA rank

1368.4 Da

XLogP3

logD₇.₄

TPSA

410 Å²

pKa

Charge pH 7.4

H-bond donors

H-bond acceptors

IC50 (HCEC)

Formula

C55H74IN3O21S4

PubChem CID

10953353

ADCdb payload

PAY0RZSDY

Hydrophobicity · logD₇.₄

hydrophilic −2+2+4 lipophilic

Bioactivity note

ADCdb (DRG0JOHND) reports payload/ADC potency against CD33+ cells with most potent IC50 ~20 pM (ML-2) and ~30 pM (MOLM-13, EoL-1); clinical objective response rate ~85% in CD33+ AML. Calicheamicin warhead induces sequence-selective double-strand DNA breaks (ADCdb lists the mechan

Dosing & regimen

Dosing

RP2D dose

3 mg/m² (max 4.5 mg)

Schedule

D1+D4+D7 induction

Route

Fractionated

Yes

n at RP2D

131

Dose basis

BSA

Trial phase

Approved

Dose-OAE available

Tox summary basis

RP2D

Ocular & expression

Ocular profile & eye-tissue target expression

Target profile

OAE any-grade

0 %

OAE grade 3+

0 %

OAE data status

documented-absent

Severity (weighted)

Keratopathy

Conjunctival

Dry eye

Blurred vision

Dominant tissue

Surface subtype

None

Grading scale

Unknown

Reversibility

Unknown

Target expression in eye tissues (HCA detection · HPA bulk)

Cornea (central)

0.07 %

Cornea (limbal)

0.03 %

Conjunctiva

0.06 %

RPE

0.46 %

Retina (HPA)

0.2 nTPM

Cross-trial comparability

Ascertainment: Symptom-driven reportingScale: UnknownDenominator: RP2D⚠ OAE rate not directly comparable across trials

Identity & registry

Identifiers, registry & notes

ADC id

gemtuzumab-ozogamicin

Approval status

FDA-approved

Approval year

2000

UniProt

P20138

ADCdb ADC

DRG0JOHND

ADCdb antibody

ANI0AZCDK

ADCdb target

TAR0OVWVF

Primary source

FDA Mylotarg label (DailyMed)

Aliases & development codes

Mylotarg; CMA-676

Notes

Hematologic target; both routes to cornea closed (no expression + hydrophilic payload). V3.1: n=131 (ALFA-0701 pivotal, basis for 2017 reapproval); prior 242 not in label.