[1]. A phase I pharmacokinetic and pharmacodynamic study of OGX-011, a 2'-methoxyethyl antisense oligonucleotide to clusterin, in patients with localized prostate cancer. J Natl Cancer Inst. 2005;97(17):1287-1296.

Custirsen is a benzopyran compound with potential antitumor activity. As a selective estrogen receptor modulator (SERM), Custirsen inhibits the proliferation of estrogen-sensitive breast cancer cells. The drug also inhibits the growth of glioblastoma cells and induces apoptosis through an estrogen receptor-independent mechanism. Custirsen is also currently under investigation for the treatment of primary brain tumors. Custirsen is a mixed-backbone antisense oligodeoxynucleotide with potential chemosensitizing activity. After administration, Custirsen blocks the translation of testosterone-suppressed prostaglandin 2 (TRPM-2). This eliminates the anti-apoptotic effect of TRPM-2, making cells more sensitive to chemotherapy and ultimately leading to tumor cell death. TRPM-2 is an anti-apoptotic cluster protein overexpressed in prostate cancer cells and associated with chemosensitivity. [hr] [strong] [Drug Indications] [strong] [br] [Investigated for the treatment of brain cancer and breast cancer.] Mechanism of Action CC-8490 is a selective estrogen receptor modulator (SERM) that inhibits the proliferation of estrogen-sensitive breast cancer cells. This drug also inhibits the growth of glioblastoma cells and induces apoptosis through an estrogen receptor-independent mechanism. Preliminary results regarding its mechanism of action in brain cancer indicate that C-8490 exerts its effects by inhibiting nuclear factor (NF)-κB and its target genes IEX-3, SOD2, IL6, and IL8. Pharmacodynamics CC-8490 is a proprietary benzopyran compound from Celgene, a novel anticancer compound currently being evaluated for its efficacy as a potential therapy for brain cancer. The National Cancer Institute has also reported its potential antitumor activity in breast cancer treatment. CC-8490 is a selective estrogen receptor modulator (SERM) that inhibits the proliferation of estrogen-sensitive breast cancer cells. Furthermore, this drug also inhibits the growth of glioblastoma cells and induces apoptosis through an estrogen receptor-independent mechanism.

C231H312N78O119P20S20

7346.17541599274

7342.999

890056-27-6

76964582

Off-white to light yellow solid powder

-10

47

171

154

468

20600

71

S=P(O)(OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3C(NC(N)=NC2=3)=O)O1)OCCOC)OP(O)(OC[C@@H]1[C@H]([C@H]([C@H](N2C(N=C(C(C)=C2)N)=O)O1)OCCOC)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(N)=NC=NC2=3)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(NC(N)=NC2=3)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C(N=C(C=C2)N)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(N)=NC=NC2=3)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(NC(N)=NC2=3)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(N)=NC=NC2=3)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(NC(N)=NC2=3)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C(NC(C(C)=C2)=O)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C(N=C(C=C2)N)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C(NC(C(C)=C2)=O)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C(NC(C(C)=C2)=O)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C(N=C(C=C2)N)=O)O1)OP(O)(OC[C@@H]1[C@H](C[C@H](N2C=NC3C(N)=NC=NC2=3)O1)OP(O)(OC[C@@H]1[C@H]([C@H]([C@H](N2C(NC(C(C)=C2)=O)=O)O1)OCCOC)OP(O)(OC[C@@H]1[C@H]([C@H]([C@H](N2C(N=C(C(C)=C2)N)=O)O1)OCCOC)OP(=O)(OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3C(N)=NC=NC2=3)O1)OCCOC)OP(O)(OC[C@@H]1[C@H]([C@H]([C@H](N2C(NC(C(C)=C2)=O)=O)O1)OCCOC)O)=S)S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)=S)O[C@@H]1[C@@H](COP(O)(O[C@@H]2[C@@H](CO)O[C@H]([C@@H]2OCCOC)N2C(N=C(C(C)=C2)N)=O)=S)O[C@H]([C@@H]1OCCOC)N1C=NC2C(N)=NC=NC1=2

RCFZILUHCNXXFY-DEDWCYLFSA-N

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1-[(2R,4S,5R)-5-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-2-[[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-(hydroxymethyl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3S,5R)-3-[[(2R,3R,4R,5R)-3-[[(2R,3R,4R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-[hydroxy-[[(2R,3R,4R,5R)-3-hydroxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphinothioyl]oxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-4-(2-methoxyethoxy)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~50 mg/mL (~6.81 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)