Physicochemical Properties
| Molecular Formula | C224H304N79O116P19S19 |
| Molecular Weight | 7157.00673389435 |
| Exact Mass | 7152.002 |
| CAS # | 1002331-21-6 |
| Related CAS # | Apatorsen sodium;915443-09-3 |
| PubChem CID | 91865088 |
| Appearance | White to off-white solid powder |
| LogP | -13.2 |
| Hydrogen Bond Donor Count | 51 |
| Hydrogen Bond Acceptor Count | 160 |
| Rotatable Bond Count | 148 |
| Heavy Atom Count | 457 |
| Complexity | 20700 |
| Defined Atom Stereocenter Count | 40 |
| SMILES | CC1=CN(C(=O)NC1=O)[C@H]2CC([C@H](O2)COP(=S)(O)OC3C[C@@H](O[C@@H]3COP(=S)(O)OC4C[C@@H](O[C@@H]4COP(=S)(O)OC5C[C@@H](O[C@@H]5COP(=S)(O)OC6C[C@@H](O[C@@H]6COP(=S)(O)OC7C[C@@H](O[C@@H]7COP(=S)(O)OC8C[C@@H](O[C@@H]8COP(=S)(O)OC9C[C@@H](O[C@@H]9COP(=S)(O)OC1C[C@@H](O[C@@H]1COP(=S)(O)OC1[C@H](O[C@H](C1OCCOC)N1C=NC2=C(N=CN=C21)N)COP(=S)(O)OC1[C@H](O[C@H](C1OCCOC)N1C=NC2=C1N=C(NC2=O)N)COP(=S)(O)OC1[C@H](O[C@H](C1OCCOC)N1C=NC2=C1N=C(NC2=O)N)COP(=S)(O)OC1[C@H](O[C@H](C1OCCOC)N1C=NC2=C1N=C(NC2=O)N)CO)N1C=C(C(=NC1=O)N)C)N1C=NC2=C1N=C(NC2=O)N)N1C=C(C(=NC1=O)N)C)N1C=NC2=C1N=C(NC2=O)N)N1C=NC2=C1N=C(NC2=O)N)N1C=C(C(=NC1=O)N)C)N1C=NC2=C1N=C(NC2=O)N)N1C=C(C(=NC1=O)N)C)OP(=S)(O)OC[C@@H]1C(C[C@@H](O1)N1C=C(C(=NC1=O)N)C)OP(=S)(O)OC[C@@H]1C(C[C@@H](O1)N1C=NC2=C1N=C(NC2=O)N)OP(=S)(O)OC[C@@H]1C(C[C@@H](O1)N1C=NC2=C1N=C(NC2=O)N)OP(=S)(O)OC[C@@H]1C(C([C@@H](O1)N1C=C(C(=O)NC1=O)C)OCCOC)OP(=S)(O)OC[C@@H]1C(C([C@@H](O1)N1C=C(C(=NC1=O)N)C)OCCOC)OP(=S)(O)OC[C@@H]1C(C([C@@H](O1)N1C=NC2=C1N=CNC2=N)OCCOC)OP(=S)(O)OC[C@@H]1C(C([C@@H](O1)N1C=C(C(=O)NC1=O)C)OCCOC)O |
| InChi Key | RMTMMKNSPRRFHW-SVAVBUBPSA-N |
| InChi Code | InChI=1S/C224H304N79O116P19S19/c1-88-46-284(216(318)257-168(88)225)129-34-97(401-420(327,439)363-60-114-102(39-134(386-114)289-52-94(7)187(306)281-222(289)324)406-421(328,440)362-56-110-98(35-130(381-110)285-47-89(2)169(226)258-217(285)319)402-422(329,441)368-63-119-107(44-139(390-119)297-81-252-147-182(297)267-211(237)276-194(147)313)411-430(337,449)372-66-121-108(45-140(392-121)298-82-253-148-183(298)268-212(238)277-195(148)314)412-431(338,450)375-69-123-154(163(357-29-21-349-13)201(396-123)292-54-96(9)189(308)283-224(292)326)414-435(342,454)377-70-124-155(162(356-28-20-348-12)200(395-124)290-51-93(6)173(230)262-221(290)323)415-436(343,455)378-72-126-157(165(359-31-23-351-15)203(398-126)300-84-247-142-175(232)243-76-245-177(142)300)417-433(340,452)374-68-122-152(305)160(354-26-18-346-10)199(394-122)291-53-95(8)188(307)282-223(291)325)111(382-129)57-364-426(333,445)407-103-40-135(293-77-248-143-178(293)263-207(233)272-190(143)309)387-116(103)61-367-423(330,442)403-99-36-131(286-48-90(3)170(227)259-218(286)320)384-113(99)59-366-428(335,447)409-105-42-137(295-79-250-145-180(295)265-209(235)274-192(145)311)391-120(105)65-371-429(336,448)410-106-43-138(296-80-251-146-181(296)266-210(236)275-193(146)312)389-118(106)62-369-424(331,443)404-100-37-132(287-49-91(4)171(228)260-219(287)321)383-112(100)58-365-427(334,446)408-104-41-136(294-78-249-144-179(294)264-208(234)273-191(144)310)388-117(104)64-370-425(332,444)405-101-38-133(288-50-92(5)172(229)261-220(288)322)385-115(101)67-373-432(339,451)416-156-125(397-202(164(156)358-30-22-350-14)299-83-246-141-174(231)242-75-244-176(141)299)71-379-437(344,456)419-159-128(400-206(167(159)361-33-25-353-17)303-87-256-151-186(303)271-215(241)280-198(151)317)74-380-438(345,457)418-158-127(399-205(166(158)360-32-24-352-16)302-86-255-150-185(302)270-214(240)279-197(150)316)73-376-434(341,453)413-153-109(55-304)393-204(161(153)355-27-19-347-11)301-85-254-149-184(301)269-213(239)278-196(149)315/h46-54,75-87,97-140,152-167,199-206,304-305H,18-45,55-74H2,1-17H3,(H,327,439)(H,328,440)(H,329,441)(H,330,442)(H,331,443)(H,332,444)(H,333,445)(H,334,446)(H,335,447)(H,336,448)(H,337,449)(H,338,450)(H,339,451)(H,340,452)(H,341,453)(H,342,454)(H,343,455)(H,344,456)(H,345,457)(H2,225,257,318)(H2,226,258,319)(H2,227,259,320)(H2,228,260,321)(H2,229,261,322)(H2,230,262,323)(H2,231,242,244)(H2,232,243,245)(H,281,306,324)(H,282,307,325)(H,283,308,326)(H3,233,263,272,309)(H3,234,264,273,310)(H3,235,265,274,311)(H3,236,266,275,312)(H3,237,267,276,313)(H3,238,268,277,314)(H3,239,269,278,315)(H3,240,270,279,316)(H3,241,271,280,317)/t97?,98?,99?,100?,101?,102?,103?,104?,105?,106?,107?,108?,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,152?,153?,154?,155?,156?,157?,158?,159?,160?,161?,162?,163?,164?,165?,166?,167?,199-,200-,201-,202-,203-,204-,205-,206-,420?,421?,422?,423?,424?,425?,426?,427?,428?,429?,430?,431?,432?,433?,434?,435?,436?,437?,438?/m1/s1 |
| Chemical Name | 1-[(2R,5R)-5-[[[(2R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[[(2R,5R)-2-[[[(2R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[[(2R,5R)-2-[[[(2R,5R)-2-[[[(2R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[[(2R,5R)-2-[[[(2R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-2-[[[(2R,5R)-2-[[[(2R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[(2R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)-4-(2-methoxyethoxy)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-[[(2R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[(2R,5R)-3-[[(2R,5R)-3-[[(2R,5R)-3-[[(2R,5R)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[hydroxy-[[(2R,5R)-3-[hydroxy-[[(2R,5R)-3-hydroxy-4-(2-methoxyethoxy)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphinothioyl]oxy-5-(6-imino-1H-purin-9-yl)-4-(2-methoxyethoxy)oxolan-2-yl]methoxy]phosphinothioyl]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-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| References |
[1]. A Randomized, Double-Blinded, Phase II Trial of Carboplatin and Pemetrexed with or without Apatorsen (OGX-427) in Patients with Previously Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer: The SPRUCE Trial. Oncologist. 2019;24(12):e1409-e1416. [2]. A randomized phase 2 study of a HSP27 targeting antisense, apatorsen with prednisone versus prednisone alone, in patients with metastatic castration resistant prostate cancer. Invest New Drugs. 2018;36(2):278-287. |
| Additional Infomation |
Apatorsen is a second generation antisense drug which in preclinical experiments, inhibits production of Heat Shock Protein 27 (Hsp27) a cell survival protein found at elevated levels in many human cancers including prostate, lung, breast, ovarian, bladder, renal, pancreatic, multiple myeloma and liver cancer. Apatorsen is a second-generation antisense oligonucleotide targeting heat shock protein 27 (Hsp27) with potential antitumor and chemosensitizing activities. Apatorsen suppresses tumor cell expression of Hsp27, which may induce tumor cell apoptosis and enhance tumor cell sensitivity to cytotoxic agents. Hsp27, a chaperone belonging to the small heat shock protein (sHsp) group of proteins, is a cytoprotective protein that supports cell survival under conditions of stress; it has been found to be over-expressed in a variety of human cancers. Drug Indication Investigated for use/treatment in cancer/tumors (unspecified). Pharmacodynamics OGX-427 significantly decreases levels of Hsp27, induces apoptosis in several human cancer cell lines, has single agent anti-tumor activity, and acts as a chemosensitizer in combination with several cytotoxic drugs including docetaxel. |
Solubility Data
| Solubility (In Vitro) | H2O : ≥ 20 mg/mL (~2.79 mM) |
| Solubility (In Vivo) |
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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1397 mL | 0.6986 mL | 1.3972 mL | |
| 5 mM | 0.0279 mL | 0.1397 mL | 0.2794 mL | |
| 10 mM | 0.0140 mL | 0.0699 mL | 0.1397 mL |