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12-O-Tetradecanoylphorbol-13-acetate

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Also known as: 16561-29-8, 12-o-tetradecanoylphorbol-13-acetate, Phorbol-12-myristate-13-acetate, 12-o-tetradecanoylphorbol 13-acetate, Phorbol ester, Tetradecanoylphorbol acetate

Molecular Formula

C₃₆H₅₆O₈

Molecular Weight

616.8 g/mol

InChI Key

PHEDXBVPIONUQT-RGYGYFBISA-N

FDA UNII

NI40JAQ945

A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

1 2D Structure

2D Structure

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

[(1S,2S,6R,10S,11R,13S,14R,15R)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate

2.1.2 InChI

InChI=1S/C36H56O8/c1-7-8-9-10-11-12-13-14-15-16-17-18-29(39)43-32-24(3)35(42)27(30-33(5,6)36(30,32)44-25(4)38)20-26(22-37)21-34(41)28(35)19-23(2)31(34)40/h19-20,24,27-28,30,32,37,41-42H,7-18,21-22H2,1-6H3/t24-,27+,28-,30-,32-,34-,35-,36-/m1/s1

2.1.3 InChI Key

PHEDXBVPIONUQT-RGYGYFBISA-N

2.1.4 Canonical SMILES

CCCCCCCCCCCCCC(=O)OC1C(C2(C(C=C(CC3(C2C=C(C3=O)C)O)CO)C4C1(C4(C)C)OC(=O)C)O)C

2.1.5 Isomeric SMILES

CCCCCCCCCCCCCC(=O)O[C@@H]1[C@H]([C@]2([C@@H](C=C(C[C@]3([C@H]2C=C(C3=O)C)O)CO)[C@H]4[C@@]1(C4(C)C)OC(=O)C)O)C

2.2 Other Identifiers

2.2.1 UNII

NI40JAQ945

2.3 Synonyms

2.3.1 MeSH Synonyms

1. 12 Myristoyl 13 Acetylphorbol

2. 12 O Tetradecanoyl Phorbol 13 Acetate

3. 12-myristoyl-13-acetylphorbol

4. 12-o-tetradecanoyl Phorbol 13-acetate

5. 13-acetate, 12-o-tetradecanoyl Phorbol

6. Acetate, Phorbol Myristate

7. Acetate, Tetradecanoylphorbol

8. Myristate Acetate, Phorbol

9. Phorbol 13-acetate, 12-o-tetradecanoyl

10. Phorbol Myristate Acetate

11. Tetradecanoylphorbol Acetate

12. Tetradecanoylphorbol Acetate, 4a Alpha Isomer

13. Tetradecanoylphorbol Acetate, 4a Alpha-isomer

2.3.2 Depositor-Supplied Synonyms

1. 16561-29-8

2. 12-o-tetradecanoylphorbol-13-acetate

3. Phorbol-12-myristate-13-acetate

4. 12-o-tetradecanoylphorbol 13-acetate

5. Phorbol Ester

6. Tetradecanoylphorbol Acetate

7. Factor A1

8. 12-tetradecanoylphorbol 13-acetate

9. Phorbol Myristate Acetate

10. Phorbol 13-acetate 12-myristate

11. Pma

12. Factor A1 (croton Oil)

13. Pma (tumor Promoter)

14. Phorbol 12-tetradecanoate 13-acetate

15. Tpa (phorbol Derivative)

16. Ccris 716

17. Pma (phorbol Ester)

18. Tpa

19. Tpa (phorbol Ester)

20. Phorbol Monoacetate Monomyristate

21. Hsdb 3542

22. 13-o-acetylphorbol 12-myristate

23. 12-o-tetradecanoyl Phorbol Acetate

24. Beta-phorbol 12-myristate 13-acetate

25. Nsc 262244

26. 12-tetradecanoylphorbol 13-monoacetate

27. 4beta-phorbol 12-myristate 13-acetate

28. Phorbol 12-myristate 13-acetate Diester

29. Chembl279115

30. Ni40jaq945

31. Chebi:37537

32. Nsc-262244

33. (1ar,1bs,4ar,7as,7bs,8r,9r,9as)-9a-acetoxy-4a,7b-dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1a,1b,4,4a,5,7a,7b,8,9,9a-decahydro-1h-cyclopropa[3,4]benzo[1,2-e]azulen-9-yl Tetradecanoate

34. Phorbol 12-myristate 13-acetate (pma)

35. Phorbol Acetate, Myristate

36. 12-o-tetradekanoylphorbol-13-acetat

37. 12-o-tetradecanoyl Phorbol-13-acetate

38. Phorbol-myristate Acetate

39. Mfcd00036736

40. Pentahydroxy-tigliadienone-monoacetate(c)monomyristate(b)

41. Yristate

42. Unii-ni40jaq945

43. 13-tetradecanoylphorbol Acetate

44. Nsc626496

45. Cocarcinogen A1

46. Cocarcinogen C3

47. Phorbol-12-myristate 13-acetate

48. Tetradecanoyl-beta-phorbol Acetate

49. 12-tetradecanoylphorbol-13-acetate

50. 5h-cyclopropa(3,4)benz(1,2-e)azulen-5-one, 1,1a-beta,1b-alpha,4,4a,7a-beta,7b,8,9,9a-decahydro-4a-alpha,7b-beta,9-alpha,9a-beta-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-beta-tetramethyl-, 9a-acetate 9-myristate

51. 12-o-tetradecanoyl-phorbol-13-acetate

52. 4beta-phorbol-12-myristate-13-acetate

53. Brn 2407201

54. Specplus_000801

55. Spectrum2_001911

56. Spectrum4_000889

57. Spectrum5_001855

58. Molmap_000041

59. Upcmld-dp069

60. 12-o-tetradekanoylphorbol-13-acetat [german]

61. Bidd:pxr0145

62. Cbiol_002014

63. Bspbio_001024

64. Kbiogr_000364

65. Kbiogr_001298

66. Kbioss_000364

67. Spectrum330004

68. Tetradecanoic Acid, 9a-(acetyloxy)-1a,1b,4,4a,5,7a,7b,8,9,9a-decahydro-4a,7b-dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1h-cyclopropa(3,4)benz(1,2-e)azulen-9-yl Ester, (1ar-(1aalpha,1bbeta,4abeta,7aalpha,7balpha,8alpha,9beta,9aalpha))-

69. Divk1c_006897

70. Schembl115567

71. Phorbol12-myristate13-acetate

72. Spbio_001902

73. 1h-cyclopropa[3,4]benz[1,2-e]azulene, Tetradecanoic Acid Deriv.

74. Gtpl2341

75. [acetoxy-dihydroxy-(hydroxymethyl)-tetramethyl-oxo-[?]yl] Tetradecanoate

76. Dtxsid5023798

77. Upcmld-dp069:001

78. Upcmld-dp069:002

79. Bcbcmap01_000182

80. Kbio1_001841

81. Kbio2_000364

82. Kbio2_002932

83. Kbio2_005500

84. Kbio3_000707

85. Kbio3_000708

86. Bio1_000300

87. Bio1_000789

88. Bio1_001278

89. Bio2_000352

90. Bio2_000832

91. Hms1362d05

92. Hms1792d05

93. Hms1990d05

94. Hms3403d05

95. Phorbol 13 Acetate 12 Myristate

96. Ex-a6920

97. Zinc8214783

98. Bdbm50099066

99. Ccg-39863

100. Nsc262244

101. Nsc262644

102. S7791

103. Akos024418767

104. Cs-6053

105. Fs-4842

106. Lmpr0104330002

107. Nsc-262644

108. Nsc-626496

109. Idi1_002107

110. Ncgc00161633-01

111. Ncgc00161633-04

112. Ncgc00161633-05

113. 4-.beta.-phorbol 12-myristate 13-oac

114. Ac-33957

115. Hy-18739

116. Myristic Acid, 9-ester With 1,1aalpha,1bbeta,4,4a,7aalpha,7b,8,9,9a-decahydro-4abeta,7balpha,9beta,9aalpha-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8alpha-tetramethyl-5h-cyclopropa(3,4)benz(1,2-e)azulen-5-one 9a-acetate, (+)-

117. Tetradecanoic Acid, (1ar,1bs,4ar,7as,7bs,8r,9r,9as)-9a-(acetyloxy)-1a,1b,4,4a,5,7a,7b,8,9,9a-decahydro-4a,7b-dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1h-cyclopropa[3,4]benz[1,2-e]azulen-9-yl Ester

118. Tetradecanoic Acid, 9a-(acetyloxy)-1a,1b,4,4a,5,7a,7b,8,9, 9a-decahydro-4a,7b-dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1h-cyclopropa(3,4)benz(1,2-e)azulen-9-yl Ester, (1ar-(1aa,1bb,4ab,7aa,7ba, 8a,9b,9aa))-

119. 12-o-tetradecanoylphorbol-13-acetate (tpa)

120. N2060

121. P1585

122. Phorbol-12-tetradecanoyl-13-acetate

123. C05151

124. 4abeta,7aalpha,7balpha,8alpha,9beta,9aalpha)]-

125. Q416716

126. W-201494

127. 12-o-tetradecanoylphorbol-13-acetate [hsdb]

128. Brd-k68552125-001-03-8

129. Brd-k68552125-001-04-6

130. Phorbol 12-myristate 13-acetate Diester [mi]

131. Phorbol-12-myristate-13-acetate - Cas 16561-29-8

132. Phorbol 12-myristate 13-acetate, Synthetic, >=98.0% (tlc)

133. Pma, For Use In Molecular Biology Applications, >=99% (tlc)

134. Phorbol 12-myristate 13-acetate, >=99% (tlc), Film Or Powder

135. 12-o-tetradecanoyl Phorbol-13-acetate;cocarcinogen A1; Cocarcinogen C3

136. (1ar,1bs,4ar,7as,7bs,8r,9r,9as)-9a-(acetyloxy)-1a,1b,4,4a,5,7a,7b,8,9,9a-decahydro-4a,7b-dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1h-cyclopropa[3,4]benz[1,2-e]azulen-9-yl Tetradecanoate

137. (1s,2s,6r,10s,11r,13s,14r,15r)-13-(acetyloxy)-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxotetracyclo[8.5.0.0^{2,6}.0^{11,13}]pentadeca-3,8-dien-14-yl Tetradecanoate

138. [(1s,2s,6r,10s,11r,13s,14r,15r)-13-acetyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] Tetradecanoate

139. 11016-13-0

140. 5h-cyclopropa(3,4)benz(1,2-e)azulen-5-one, 1,1a-beta,1b-alpha,4,4a,7a-beta,7b,8,9,9a-decahydro-4a-alpha,7b-beta,9-alpha,9a-beta-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-beta-tetramethyl-, 9a-acetate 9-m

141. Myristic Acid, 9-ester With 1,1a-alpha,1b-beta,4,4a,7a-alpha,7b,8,9,9a-decahydro-4a-beta,7b-alpha,9-beta,9a-alpha-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-alpha-tetramethyl-5h-cyclopropa(3,4)benz(1,2-e)azulen-5-one, 9a-acetate

142. Myristic Acid, 9-ester With 1,1aalpha,1bbeta,4,4a,7aalpha,7b,8,9,9a-decahydro-4abeta,7balpha,9beta,9aalpha-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8alpha-tetramethyl-5h-cyclopropa[3,4]benz[1,2-e]azulen-5

143. Tetradecanoic Acid, (1ar,1bs,4ar,7as,7bs,8r,9r,9as)-9a-(acetyloxy)-1a,1b,4,4a,5,7a,7b,8,9,9a-decahydro-4a,7b-dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1h-cyclopropa[3,4]benz[1,2-e]azulen-9

144. Tetradecanoic Acid, 9a-(acetyloxy)-1a,1b,4,4a,5,7a,7b,8,9,9a-decahydro-4a,7b-dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1h-cyclopropa[3,4]benz[1,2-e]azulen-9-yl Ester, [1ar-(1aalpha,1bbeta,

145. Tetradisant-[[4-(1, 1-oxideomega.-[2-(dodecylthio)ethoxy]-,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-, (8s-cis)-, Mixt. With Denatured Calf Thymus Dnaa, (2s-cis)-, Compd. With Sulfinylbis[methane] (2:1)2s-cis)-1:9)

2.4 Create Date

2005-03-26

3 Chemical and Physical Properties

Molecular Formula	C₃₆H₅₆O₈
Molecular Weight	616.8 g/mol
XLogP3	6.5
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	17
Exact Mass	616.39751874 g/mol
Monoisotopic Mass	616.39751874 g/mol
Topological Polar Surface Area	130 Å²
Heavy Atom Count	44
Formal Charge	0
Complexity	1150
Isotope Atom Count	0
Defined Atom Stereocenter Count	8
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Therapeutic Uses

/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. 12-O-Tetradecanoylphorbol-13-acetate is included in the database.

NIH/NLM; ClinicalTrials.Gov. Available from, as of March 17, 2016: https://clinicaltrials.gov/ct2/results?term=12-O-TETRADECANOYLPHORBOL-13-ACETATE&Search=Search

/EXPL THER/ Phorbol esters activate protein kinase C and modulate a variety of downstream cell signaling pathways. 12-O-tetradecanoylphorbol-13-acetate (TPA) is a phorbol ester that induces differentiation or apoptosis in a variety of cell lines at low concentrations. A phase I dose escalation trial of TPA was undertaken for patients with relapsed or refractory malignancies. The starting dose was 0.063 mg/sq m and most patients were treated with an intravenous infusion of TPA on days 1-5 and 8-12 followed by a 2-week rest period prior to retreatment. Thirty-five patients were treated. A biological assay was used to monitor levels of TPA-like activity in the blood after treatment. Serious adverse events included individual episodes of gross hematuria, a grand mal seizure, syncope, and hypotension. Many patients had transient fatigue, mild dyspnea, fever, rigors, and muscular aches shortly after the infusion. Dose-limiting toxicities included syncope and hypotension at a dose of 0.188 mg/sq m. Only a single patient had evidence of tumor response. These studies establish 0.125 mg/sq m as the maximally tolerated dose when TPA is administered on this schedule.

PMID:16231182 Schaar D et al; Cancer Chemother Pharmacol 57 (6): 789-95 (2006)

5 Pharmacology and Biochemistry

5.1 MeSH Pharmacological Classification

Carcinogens

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. (See all compounds classified as Carcinogens.)

5.2 Absorption, Distribution and Excretion

...Mouse skin localization expt...determined that at 3-6 hr after skin application /with tritiated PMA/ the keratin layer just above basal cells was highly labeled, & sebaceous glands & hair follicles were moderately labeled. After 48 hr there was still some labeling in sebaceous glands & hair follicles. Half-life of...promoter was close to 24 hr.

Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976., p. 38

5.3 Metabolism/Metabolites

...the major pathway in the metabolism of TPA is the hydrolysis of the two ester groups, ... in the rodent skin model all hydrolytic products lack tumor promoting activity, the major toxicological effect of TPA. The metabolic hydrolysis requires the activity of esterases, the activity of which differs between tissues and species. ... both ester groups of TPA can be hydrolysed in mouse skin and in cultured cells, giving rise to the monoesters 12-tetradecanoylphorbol and phorbol-13-acetate, as well as the product of complete hydrolysis, i.e. phorbol. Reduction of the keto group at C-3 was identified as a further metabolic pathway in mouse skin. ... Noteworthy, no other metabolites were detected in the microsomal incubations, suggesting that cytochrome 450-mediated oxidative metabolism is not involved in TPA metabolism. Ester group hydrolysis was also the only metabolic reaction observed in various cultured cells ... .