Peptide Information

General Information of This Peptide
Peptide ID
PEP00175
Peptide Name
Unique variant of pHLIP
Structure
Sequence
ADDONPWRAYLDLLFPTDTILLDLLWCG
Peptide Type
Linear
Receptor Name
DNA topoisomerase 1 (TOP1)
  Receptor Info 
PDC Transmembrane Types Cell targeting peptides (CTPs)
Distribution
Acidity is produced not only by cancerous tissue, but also by any tissue that is experiencing hypoxia: the lack of oxygen in the tissue triggers cells to switch to a high rate of the anaerobic, glycolytic energy production pathway, consequently resulting in acidification. pHLIPs have been shown to target infections in lungs, inflammatory arthritis, and ischemic myocardium, a consequence of heart disease, and could be used for diagnosis and treatment thereof. It is also possible that pHLIPs could be used as targeted treatment in ischemic strokes. In contrast to diseased tissue, healthy tissue is typically not associated with increased acidity except in the gastrointestinal tract and kidney, the pHs of which might be regulated by the implementation of a special diet or supplementary drinks if their acidity proves problematic.
Formula
C159H236N36O44S
Isosmiles
[H]NC(=O)C[C@H](NC(=O)[C@H](CCCCNC(=O)[C@@H]1N=CC[C@H]1C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N[H])C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1cn([H])c2ccccc12)C(=O)N[C@@H](CCC/N=C(/N)N[H])C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccc(O[H])cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@]([H])(C(=O)N[C@@H](CC(=O)O)C(=O)N[C@]([H])(C(=O)N[C@]([H])(C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cn([H])c2ccccc12)C(=O)N[C@@H](CS[H])C(=O)NCC(=O)O)[C@@H](C)CC)[C@@H](C)O[H])[C@@H](C)O[H]
InChI
InChI=1S/C159H236N36O44S/c1-22-83(16)128(154(235)186-106(61-82(14)15)141(222)176-103(58-79(8)9)139(220)182-112(69-123(204)205)148(229)179-100(55-76(2)3)136(217)175-102(57-78(6)7)138(219)181-108(64-91-72-167-96-39-28-26-37-94(91)96)145(226)190-117(75-240)133(214)169-74-126(210)211)191-156(237)130(88(21)197)192-150(231)114(71-125(208)209)187-155(236)129(87(20)196)193-152(233)119-44-34-54-195(119)157(238)115(63-89-35-24-23-25-36-89)188-142(223)105(60-81(12)13)177-137(218)101(56-77(4)5)180-149(230)113(70-124(206)207)183-140(221)104(59-80(10)11)178-143(224)107(62-90-45-47-93(198)48-46-90)174-132(213)86(19)170-134(215)99(42-32-51-166-159(162)163)172-144(225)109(65-92-73-168-97-40-29-27-38-95(92)97)185-151(232)118-43-33-53-194(118)158(239)116(66-120(161)199)189-135(216)98(41-30-31-50-165-153(234)127-84(17)49-52-164-127)171-146(227)111(68-122(202)203)184-147(228)110(67-121(200)201)173-131(212)85(18)160/h23-29,35-40,45-48,52,72-73,76-88,98-119,127-130,167-168,196-198,240H,22,30-34,41-44,49-51,53-71,74-75,160H2,1-21H3,(H2,161,199)(H,165,234)(H,169,214)(H,170,215)(H,171,227)(H,172,225)(H,173,212)(H,174,213)(H,175,217)(H,176,222)(H,177,218)(H,178,224)(H,179,229)(H,180,230)(H,181,219)(H,182,220)(H,183,221)(H,184,228)(H,185,232)(H,186,235)(H,187,236)(H,188,223)(H,189,216)(H,190,226)(H,191,237)(H,192,231)(H,193,233)(H,200,201)(H,202,203)(H,204,205)(H,206,207)(H,208,209)(H,210,211)(H4,162,163,166)/t83-,84+,85-,86-,87+,88+,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,127+,128-,129-,130-/m0/s1
InChIKey
UUNZFLYWPMXOIH-XGYFDBJRSA-N
Pharmaceutical Properties
Molecule Weight
3387.912
Polar area
1259.16
Complexity
3385.705686
xlogp Value
-5.0611
Heavy Count
240
Rot Bonds
107
Hbond acc
42
Hbond Donor
42
Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
CBX-12 [Phase 2]
 PDC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Tumor Growth Inhibition value (TGI)
58.10%
Administration Time 23 days
Administration Dosage 5 mg/kg
Evaluation Method Tumor volume detection
Description
Combination treatment significantly inhibited tumor growth without significant toxicity in both mouse xenografts compared with CBX-12 and ceralasertib monotherapy without significant toxicity.
In Vivo Model HCT-116 xenografts
Experiment 2 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Tumor Growth Inhibition value (TGI)
76.50%
Administration Time 35 days
Administration Dosage 10 mg/kg
Evaluation Method Tumor volume detection
Description
Combination treatment significantly inhibited tumor growth without significant toxicity in both mouse xenografts compared with CBX-12 and ceralasertib monotherapy without significant toxicity.
In Vivo Model MDA-MB-231 xenografts
Experiment 3 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Tumor Growth Inhibition value (TGI)
81.40%
Administration Time 23 days
Administration Dosage 5 mg/kg with ceralasertib 25 mg/kg
Evaluation Method Tumor volume detection
Description
Combination treatment significantly inhibited tumor growth without significant toxicity in both mouse xenografts compared with CBX-12 and ceralasertib monotherapy without significant toxicity.
In Vivo Model HCT-116 xenografts
Experiment 4 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Tumor Growth Inhibition value (TGI)
95%
Administration Time 35 days
Administration Dosage 10 mg/kg with ceralasertib 25 mg/kg
Evaluation Method Tumor volume detection
Description
Combination treatment significantly inhibited tumor growth without significant toxicity in both mouse xenografts compared with CBX-12 and ceralasertib monotherapy without significant toxicity.
In Vivo Model MDA-MB-231 xenografts
Experiment 5 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Survival rate
60 mm3
Administration Time 45 days
Administration Dosage 5 mg/kg
Description
Combination treatment significantly inhibited tumor growth without significant toxicity in both mouse xenografts compared with CBX-12 and ceralasertib monotherapy without significant toxicity.
In Vivo Model HCT-116 xenografts
Experiment 6 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Survival rate
75 mm3
Administration Time 42 days
Administration Dosage 10 mg/kg
Description
Combination treatment significantly inhibited tumor growth without significant toxicity in both mouse xenografts compared with CBX-12 and ceralasertib monotherapy without significant toxicity.
In Vivo Model MDA-MB-231 xenografts
Experiment 7 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Survival rate
100 mm3
Administration Time 42 days
Administration Dosage 10 mg/kg with ceralasertib 25 mg/kg
Description
Combination treatment significantly inhibited tumor growth without significant toxicity in both mouse xenografts compared with CBX-12 and ceralasertib monotherapy without significant toxicity.
In Vivo Model MDA-MB-231 xenografts
Experiment 8 Reporting the Activity Data of This PDC [1]
Indication Tumor
Efficacy Data Survival rate
100 mm3
Administration Time 45 days
Administration Dosage 5 mg/kg with ceralasertib 25 mg/kg
Description
Combination treatment significantly inhibited tumor growth without significant toxicity in both mouse xenografts compared with CBX-12 and ceralasertib monotherapy without significant toxicity.
In Vivo Model HCT-116 xenografts
References
Ref 1 TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor. Mol Cancer Ther. 2022 Jul 5;21(7):1090-1102. doi: 10.1158/1535-7163.MCT-21-1000.