Payload Information
General Information of This Payload
| Payload ID | PAY0HFZDV |
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| Name | dmDNA31 |
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| Synonyms |
Dimethylaminopiperidyl-rifa; Q5KH60X1LL; UNII-Q5KH60X1LL; DMDNA31; 1',4-Didehydro-1-deoxy-5'-(4-(dimethylamino)-1-piperidinyl)-1,4-dihydro-3'-hydroxy-1-oxorifamycin VIII; Rifamycin VIII, 1',4-didehydro-1-deoxy-5'-(4-(dimethylamino)-1-piperidinyl)-1,4-dihydro-3'-hydroxy-1-oxo-; 845625-44-7; SCHEMBL16274472
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| Target | DNA-directed RNA polymerase II subunit RPB1 (POLR2A) | |||||
| Structure |
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| Formula | C50H62N4O13 |
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| Isosmiles | C[C@H]1/C=C/C=C(\C(=O)NC2=C3C(=C4C(=C(C(=C5C4=C([C@](O5)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)O)C)O)C2=O)N=C6C(=CC(=CC6=O)N7CCC(CC7)N(C)C)O3)/C |
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| InChI |
InChI=1S/C50H62N4O13/c1-23-13-12-14-24(2)49(62)52-40-44(60)36-35(39-47(40)66-34-22-31(21-32(56)38(34)51-39)54-18-15-30(16-19-54)53(9)10)37-46(28(6)43(36)59)67-50(8,48(37)61)64-20-17-33(63-11)25(3)45(65-29(7)55)27(5)42(58)26(4)41(23)57/h12-14,17,20-23,25-27,30,33,41-42,45,57-59,61H,15-16,18-19H2,1-11H3,(H,52,62)/b13-12+,20-17+,24-14-/t23-,25+,26+,27+,33-,41-,42+,45+,50-/m0/s1
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| InChIKey |
GBSDCXVMKJSZDN-AWHPPKCISA-N
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| IUPAC Name |
[(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-30-[4-(dimethylamino)piperidin-1-yl]-2,6,15,17-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-23,32,37-trioxo-8,27,38-trioxa-24,34-diazahexacyclo[23.11.1.14,7.05,36.026,35.028,33]octatriaconta-1,3,5,9,19,21,25,28,30,33,35-undecaen-13-yl] acetate
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| Pharmaceutical Properties | Molecule Weight |
927 |
Polar area |
226 |
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Complexity |
2490 |
xlogp Value |
3.3 |
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Heavy Count |
67 |
Rot Bonds |
5 |
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Hbond acc |
16 |
Hbond Donor |
5 |
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Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
RG7861 [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Patients Enrolled |
Eligible participants are healthy adults (BMI 18-32 kg/m2) with normal clinical/lab parameters, while exclusions encompass recent antibiotic use, vaccination, substance abuse, blood donation, pregnancy, HIV/HBV/HCV positivity, malignancy history (except non-melanoma skin cancer), and rifamycin hypersensitivity. Strict contraceptive measures are required.
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| Administration Dosage |
Participants will receive DSTA4637S intravenously on Day 1.
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| Related Clinical Trial | |||||
| NCT Number | NCT02596399 | Phase Status | PHASE1 | ||
| Clinical Description |
A PHASE I, RANDOMIZED, DOUBLE-BLIND,PLACEBO-CONTROLLED, SINGLE-ASCENDING DOSE STUDY TO INVESTIGATE THE SAFETY,TOLERABILITY, AND PHARMACOKINETICS OF DSTA4637S IN HEALTHY VOLUNTEERS
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| Primary Endpoint |
The study evaluates safety by monitoring adverse events (AEs) in participants receiving DSTA4637S, with data collected up to Day 85 post-treatment.
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| Other Endpoint |
Pharmacokinetic analysis includes plasma/serum concentration measurements of DSTA4637S and anti-drug antibodies (ATAs), assessed longitudinally up to Day 85 to characterize drug exposure and immunogenicity.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Eligible participants must have a BMI of 18-40 kg/m2 and confirmed S. aureus bacteremia (positive culture within 120 hours) requiring ≥4 weeks of standard IV antibiotics. Key exclusions include unresected intravascular catheters, rifampicin-resistant S. aureus, prosthetic joint/vertebral infections, Child-Pugh B/C cirrhosis, polymicrobial bacteremia, immunosuppression, liver disease, abnormal ECG, recent biologic/experimental therapy, or anticipated cardiac surgery within 3 days post-randomization. Rifamycin-class antibiotics (except rifaximin) are prohibited during the study.
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| Administration Dosage |
DSTA4637S will be administered as an IV infusion at 3 dose levels.
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| Related Clinical Trial | |||||
| NCT Number | NCT03162250 | Phase Status | PHASE1 | ||
| Clinical Description |
A Phase IB, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S in Patients With Staphylococcus Aureus Bacteremia Receiving Standard-of-Care Antibiotics
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| Primary Endpoint |
The study assesses safety by tracking the percentage of participants experiencing adverse events (AEs) over a monitoring period extending up to approximately 156 days from baseline.
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| Other Endpoint |
Pharmacokinetic evaluations include measurements of Antibody-Conjugated dmDNA31 and DSTA4637S Total Antibody in plasma and serum, respectively, along with unconjugated dmDNA31 levels, all monitored from baseline up to approximately 156 days. Immunogenicity is evaluated via the percentage of participants developing anti-therapeutic antibodies (ATAs) to DSTA4637S during the same timeframe.
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References