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Purity: ≥98%
Delcasertib (also known as KAI-9803 and BMS-875944) is a potent and selective δ-protein kinase C (δPKC) inhibitor that is composed of a peptide derived from the δV1-1 portion of δPKC (termed 'cargo peptide'), conjugated reversibly to the cell-penetrating peptide 11-amino acid, arginine-rich sequence of the HIV type 1 transactivator protein (TAT₄₇₋₅₇; termed 'carrier peptide') via a disulfide bond. KAI-9803 administration at the end of ischemia has been found to reduce cardiac damage caused by ischemia-reperfusion in a rat model of acute myocardial infarction. In the study presented here, we examined the TAT₄₇₋₅₇-mediated distribution of KAI-9803 in rats after a single intravenous bolus administration (1 mg/kg). ¹⁴C-KAI-9803 was rapidly delivered to many tissues, including the heart (1.21 μg eq/g tissue), while being quickly cleared from the systemic circulation. The microautoradiography analysis showed that ¹⁴C-KAI-9803 was effectively delivered into various cells, including cardiac myocytes and cardiac endothelial cells within 1 min after dosing. The tissue distribution of ¹²⁵I-labeled KAI-9803 was compared to that of ¹²⁵I-labeled cargo peptide; this comparison demonstrated that the distribution of KAI-9803 to tissues such as the liver, kidney, and heart was facilitated by the reversible conjugation to TAT₄₇₋₅₇. In an in vitro cardiomyocyte study, the extent of ¹²⁵I-KAI-9803 internalization was greater at 37°C than that at 4°C, whereas the internalization of the ¹²⁵I-cargo peptide at 37°C was not observed, indicating that the uptake of ¹²⁵I-KAI-9803 into the cardiomyocytes was mediated by the TAT₄₇₋₅₇ carrier. Our studies demonstrated that after a single intravenous administration, KAI-9803 can be delivered into the target cells in the liver, kidney, and heart by a TAT₄₇₋₅₇-mediated mechanism.
| ln Vitro |
Delcasertib (KAI-9803) is composed of an 11-amino acid cell-penetrating peptide, HIV type 1 transactivator protein (TAT47-57; referred to as the "carrier peptide"), which is a selective inhibitory peptide of delta-protein kinase C (δPKC) that is derived from the deltaV1-1 moiety of deltaPKC and reversibly conjugated to a peptide that is reversibly conjugated to a cell-penetrating peptide [1].
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| ln Vivo |
In mouse liver, kidney, lung, heart, and brain, delcasertib (KAI-9803, single intraperitoneal injection) specifically inhibits PKC translocation [1]. Research has indicated that administering Delcasertib (KAI-9803) towards the end of ischemia can lessen the damage that ischemia-reperfusion causes to the heart in a rat model of acute myocardial infarction [1]. Patients having angioplasty following an acute myocardial infarction have been examined for the prevention of reperfusion injury with delcasertib (KAI-9803) [2].
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| Animal Protocol |
Animal/Disease Models: Sixweeks old male Crl:CD(SD) rats [1].
Doses: 1 mg/kg (pharmacokinetic/PK/PK analysis). Route of Administration: Through the femoral vein. Experimental Results: Reversible conjugation to TAT47-57 promoted distribution to tissues such as liver, kidney, and heart. |
| References |
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| Additional Infomation |
Drug Indication
Investigated for use/treatment in myocardial infarction. |
| Molecular Formula |
C120H199N45O34S2
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|---|---|
| Molecular Weight |
2880.27518010139
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| Exact Mass |
2879.47
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| CAS # |
949100-39-4
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| Related CAS # |
Delcasertib hydrochloride
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| PubChem CID |
56843747
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| Appearance |
White to off-white solid powder
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| LogP |
-19.7
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| Hydrogen Bond Donor Count |
53
|
| Hydrogen Bond Acceptor Count |
46
|
| Rotatable Bond Count |
108
|
| Heavy Atom Count |
201
|
| Complexity |
6270
|
| Defined Atom Stereocenter Count |
21
|
| SMILES |
S(C[C@@H](C(N[C@@H](CC1C=CC(=CC=1)O)C(NCC(N[C@@H](CCCNC(=N)N)C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(=O)O)CCCNC(=N)N)=O)CCCNC(=N)N)=O)CCCNC(=N)N)=O)CCC(N)=O)=O)CCCNC(=N)N)=O)CCCNC(=N)N)=O)CCCCN)=O)CCCCN)=O)=O)=O)=O)N)SC[C@@H](C(N[C@@H](CO)C(N[C@@H](CC1C=CC=CC=1)C(N[C@@H](CC(N)=O)C(N[C@@H](CO)C(N[C@@H](CC1C=CC(=CC=1)O)C(N[C@@H](CCC(=O)O)C(N[C@H](C(NCC(N[C@@H](CO)C(N[C@H](C(=O)O)CC(C)C)=O)=O)=O)CC(C)C)=O)=O)=O)=O)=O)=O)=O)N
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| InChi Key |
XPXZTVWPRKJTAA-PJKOMPQUSA-N
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| InChi Code |
InChI=1S/C120H199N45O34S2/c1-61(2)48-80(96(179)145-55-92(174)148-86(56-166)110(193)163-85(114(198)199)49-62(3)4)159-106(189)78(37-39-93(175)176)156-107(190)83(52-65-30-34-67(170)35-31-65)161-112(195)88(58-168)165-109(192)84(53-90(126)172)162-108(191)82(50-63-18-6-5-7-19-63)160-111(194)87(57-167)164-95(178)69(124)60-201-200-59-68(123)94(177)158-81(51-64-28-32-66(169)33-29-64)97(180)146-54-91(173)147-70(22-12-42-139-115(127)128)98(181)149-71(20-8-10-40-121)99(182)150-72(21-9-11-41-122)100(183)151-73(23-13-43-140-116(129)130)101(184)152-75(25-15-45-142-118(133)134)103(186)155-77(36-38-89(125)171)105(188)154-74(24-14-44-141-117(131)132)102(185)153-76(26-16-46-143-119(135)136)104(187)157-79(113(196)197)27-17-47-144-120(137)138/h5-7,18-19,28-35,61-62,68-88,166-170H,8-17,20-27,36-60,121-124H2,1-4H3,(H2,125,171)(H2,126,172)(H,145,179)(H,146,180)(H,147,173)(H,148,174)(H,149,181)(H,150,182)(H,151,183)(H,152,184)(H,153,185)(H,154,188)(H,155,186)(H,156,190)(H,157,187)(H,158,177)(H,159,189)(H,160,194)(H,161,195)(H,162,191)(H,163,193)(H,164,178)(H,165,192)(H,175,176)(H,196,197)(H,198,199)(H4,127,128,139)(H4,129,130,140)(H4,131,132,141)(H4,133,134,142)(H4,135,136,143)(H4,137,138,144)/t68-,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-/m0/s1
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| Chemical Name |
(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-[[(2R)-2-amino-3-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-oxopropyl]disulfanyl]propanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoic acid
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| Synonyms |
KAI-9803; BMS-875944; KAI 9803; BMS 875944; KAI9803; BMS875944
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~34.72 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.69 mg/mL (2.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 76.9 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (0.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (0.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3472 mL | 1.7359 mL | 3.4719 mL | |
| 5 mM | 0.0694 mL | 0.3472 mL | 0.6944 mL | |
| 10 mM | 0.0347 mL | 0.1736 mL | 0.3472 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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