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Signaling Pathways

The antibody-drug conjugate (ADC), a humanized or human monoclonal antibody conjugated with highly cytotoxic small molecules (payloads) through chemical linkers, is a novel therapeutic format and has great potential to make a paradigm shift in cancer chemotherapy. The three components of the ADC together give rise to a powerful oncolytic agent capable of delivering normally intolerable cytotoxins directly to cancer cells, which then internalize and release the cell-destroying drugs. At present, two ADCs, Adcetris and Kadcyla, have received regulatory approval with >40 others in clinical development.

ADCs are administered intravenously in order to prevent the mAb from being destroyed by gastric acids and proteolytic enzymes. The mAb component of the ADC enables it to circulate in the bloodstream until it finds and binds to tumor-specific cell surface antigens present on target cancer cells. Linker chemistry is an important determinant of the safety, specificity, potency and activity of ADCs. Linkers are designed to be stable in the blood stream (to conform to the increased circulation time of mAbs) and labile at the cancer site to allow rapid release of the cytotoxic drug. First generation ADCs made use of early cytotoxins such as the anthracycline, doxorubicin or the anti-metabolite/antifolate agent, methotrexate. Current cytotoxins have far greater potency and can be divided into three main groups: auristatins, maytansines and calicheamicins.

The development of site-specific conjugation methodologies for constructing homogeneous ADCs is an especially promising path to improving ADC design, which will open the way for novel cancer therapeutics.

References:

[1] Tsuchikama K, et al. Protein Cell. 2016 Oct 14. DOI:10.1007/s13238-016-0323-0.

[2] Peters C, et al. Biosci Rep. 2015 Jun 12;35(4). pii: e00225. doi: 10.1042/BSR20150089.

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  1. Bestell-Nr. Artikelname Informationen
  2. GC19789 Hyaluronidase

     Hyaluronidase;>300u/mg

     Hyaluronidase  Chemical Structure
  3. GC19566 N-Nitrosodiethylamine  N-Nitrosodiethylamine  Chemical Structure
  4. GC50569 NLRP3-IN-2

    NLRP3 inflammasome inhibitor

     NLRP3-IN-2  Chemical Structure
  5. GC63267 α-​Chaconine  α-​Chaconine  Chemical Structure
  6. GC45195 α,β-Methyleneadenosine 5'-triphosphate (sodium salt)

    α,β-Methyleneadenosine 5'-triphosphate (αβ-methylene ATP) is a phosphonic analog of ATP that is characterized by the replacement of the bridging oxygen atom between the α- and β-phosphate groups with methylene.

    α,β-Methyleneadenosine 5'-triphosphate (sodium salt)  Chemical Structure
  7. GC45194 α-(difluoromethyl)-DL-Arginine

    Bacteria synthesize the cellular growth factor putrescine through a number of pathways.

    α-(difluoromethyl)-DL-Arginine  Chemical Structure
  8. GC65446 α-Amyrin acetate α-Amyrin acetate  Chemical Structure
  9. GC63268 α-Amyrin palmitate α-Amyrin palmitate  Chemical Structure
  10. GC63269 α-Conotoxin PIA TFA α-Conotoxin PIA TFA  Chemical Structure
  11. GC63723 α-Conotoxin PnIA TFA α-Conotoxin PnIA TFA  Chemical Structure
  12. GC39464 α-Cyclodextrin α-Cyclodextrin  Chemical Structure
  13. GC45204 α-Ecdysone

    α-Ecdysone is a prohormone of 20-hydroxy ecdysone, an insect-molting, ecdysteroid hormone.

    α-Ecdysone  Chemical Structure
  14. GC38042 α-Factor Mating Pheromone, yeast (TFA) α-Factor Mating Pheromone, yeast (TFA)  Chemical Structure
  15. GC45206 α-GalCer analog 8

    α-Galactosylceramide analog 8 (α-GalCer analog 8) is a triazole derivative of α-galactosylceramide.

    α-GalCer analog 8  Chemical Structure
  16. GC45207 α-hydroxy Farnesyl Phosphonic Acid α-hydroxy Farnesyl phosphonic acid is a nonhydrolyzable analog of farnesyl pyrophosphate which acts as a competitive inhibitor of farnesyl transferase (FTase). α-hydroxy Farnesyl Phosphonic Acid  Chemical Structure
  17. GC45208 α-hydroxy Metoprolol α-hydroxy Metoprolol is an active metabolite of the β1-adrenergic receptor blocker metoprolol. α-hydroxy Metoprolol  Chemical Structure
  18. GC45210 α-Linolenic Acid (sodium salt) α-Linolenic acid (ALA) is an essential fatty acid found in leafy green vegetables. α-Linolenic Acid (sodium salt)  Chemical Structure
  19. GC45601 α-Linolenic Acid ethyl ester-d5   α-Linolenic Acid ethyl ester-d5  Chemical Structure
  20. GC45602 α-Linolenic Acid-d5 MaxSpec• Standard   α-Linolenic Acid-d5 MaxSpec• Standard  Chemical Structure
  21. GC63749 α-Lipoic Acid-d5 α-Lipoic Acid-d5  Chemical Structure
  22. GC64563 α-Methylserotonin α-Methylserotonin  Chemical Structure
  23. GC45213 α-NETA Choline acetyltransferase (ChAT) mediates the synthesis of the neurotransmitter acetylcholine from acetyl-CoA and choline. α-NETA  Chemical Structure
  24. GC38287 α-Pyridone α-Pyridone  Chemical Structure
  25. GC63941 α-Solanine α-Solanine  Chemical Structure
  26. GC63615 α-Thujone α-Thujone  Chemical Structure
  27. GC37980 α-Tocopherol phosphate α-Tocopherol phosphate  Chemical Structure
  28. GC45224 α-Truxillic Acid

    α-Truxillic acid can be formed by the dimerization of two molecules of α-trans-cinnamic acid.

    α-Truxillic Acid  Chemical Structure
  29. GC38873 α2β1 Integrin Ligand Peptide TFA α2β1 Integrin Ligand Peptide TFA  Chemical Structure
  30. GC62380 αvβ1 integrin-IN-1 αvβ1 integrin-IN-1  Chemical Structure
  31. GC62566 αvβ1 integrin-IN-1 TFA αvβ1 integrin-IN-1 TFA  Chemical Structure
  32. GC64932 αvβ5 integrin-IN-1 αvβ5 integrin-IN-1  Chemical Structure
  33. GC49467 β-Aescin A triterpenoid saponin with diverse biological activities β-Aescin  Chemical Structure
  34. GC63273 β-Amyloid (1-14),mouse,rat β-Amyloid (1-14),mouse,rat  Chemical Structure
  35. GC63274 β-Amyloid (1-42), (rat/mouse) (TFA) β-Amyloid (1-42), (rat/mouse) (TFA)  Chemical Structure
  36. GC37984 β-Amyloid (1-42), rat β-Amyloid (1-42), rat  Chemical Structure
  37. GC61394 β-Amyloid (1-42), rat TFA β-Amyloid (1-42), rat TFA  Chemical Structure
  38. GC37991 β-Amyloid 15-21 β-Amyloid 15-21  Chemical Structure
  39. GC45603 β-Amyrin   β-Amyrin  Chemical Structure
  40. GC45225 β-Apooxytetracycline β-Apooxytetracycline is a potential impurity found in commercial preparations of oxytetracycline. β-Apooxytetracycline  Chemical Structure
  41. GC60391 β-Casomorphin, bovine TFA β-Casomorphin, bovine TFA  Chemical Structure
  42. GC61484 β-Casomorphin, human TFA β-Casomorphin, human TFA  Chemical Structure
  43. GC62432 β-catenin-IN-2 β-catenin-IN-2  Chemical Structure
  44. GC63275 β-Cryptoxanthin β-Cryptoxanthin  Chemical Structure
  45. GC63276 β-Cyclocitral β-Cyclocitral  Chemical Structure
  46. GC45228 β-Cyclodextrin β-Cyclodextrin (β-CD) is a cyclic oligosaccharide that contains seven D-(+)-glucopyranose units and has been used to improve the aqueous solubility of various compounds, especially those containing a phenyl group. β-Cyclodextrin  Chemical Structure
  47. GC63277 β-Cyclogeraniol β-Cyclogeraniol  Chemical Structure
  48. GC45232 β-D-Glucosamine Pentaacetate β-D-Glucosamine pentaacetate is an N-acetylglucosamine derivative that has been shown to promote hyaluronic acid production. β-D-Glucosamine Pentaacetate  Chemical Structure
  49. GC63278 β-D-Glucose pentaacetate β-D-Glucose pentaacetate  Chemical Structure
  50. GC45230 β-Defensin-3 (human) (trifluoroacetate salt) β-Defensin-3 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. β-Defensin-3 (human) (trifluoroacetate salt)  Chemical Structure
  51. GC45231 β-Defensin-4 (human) (trifluoroacetate salt) β-Defensin-4 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts. β-Defensin-4 (human) (trifluoroacetate salt)  Chemical Structure
  52. GC45234 β-Endorphin (1-27) (human) (trifluoroacetate salt) β-Endorphin (1-27) is an endogenous peptide that binds to μ-, δ-, and κ-opioid receptors (Kis = 5.31, 6.17, and 39.82 nM, respectively, in COS-1 cells expressing rat receptors). β-Endorphin (1-27) (human) (trifluoroacetate salt)  Chemical Structure
  53. GA24007 β-Endorphin (30-31) (bovine, camel, mouse, ovine) The dipeptide Gly-Gln, which is naturally derived from the posttranslational processing of β-endorphin, exhibited an inhibitory action on cell firing when applied iontophoretically to brainstem neurons in the rat. Moreover, it seems to be a neurotrophic regulator of acetylcholinesterase in the mammalian sympathetic ganglion. Gly-Gln suppressed morphine withdrawal symptoms in rats. Gly-Gln has found use as a Gln source in parenteral nutrition, see also G-1210. β-Endorphin (30-31) (bovine, camel, mouse, ovine)  Chemical Structure
  54. GC45236 β-Endorphin (rat) β-Endorphin (β-EP) is an endogenous opioid neuropeptide with diverse biological activities. β-Endorphin (rat)  Chemical Structure
  55. GC38030 β-Endorphin, equine (TFA) β-Endorphin, equine (TFA)  Chemical Structure
  56. GC64430 β-Glucuronidase-IN-1 β-Glucuronidase-IN-1  Chemical Structure
  57. GC62551 β-Hydroxypropiovanillone β-Hydroxypropiovanillone  Chemical Structure
  58. GC49647 β-Hyodeoxycholic Acid (hydrate) A 3β epimer of hyodeoxycholic acid β-Hyodeoxycholic Acid (hydrate)  Chemical Structure
  59. GC64619 β-Ionone β-Ionone  Chemical Structure
  60. GC62235 β-Lactamase-IN-2 β-Lactamase-IN-2  Chemical Structure
  61. GC38007 β-Melanocyte Stimulating Hormone (MSH), human TFA β-Melanocyte Stimulating Hormone (MSH), human TFA  Chemical Structure
  62. GC45604 β-Rubromycin   β-Rubromycin  Chemical Structure
  63. GC38008 β-Zearalenol β-Zearalenol  Chemical Structure
  64. GC61462 γ-1-Melanocyte Stimulating Hormone (MSH), amide γ-1-Melanocyte Stimulating Hormone (MSH), amide  Chemical Structure
  65. GC38010 γ-Aminobutyric acid γ-Aminobutyric acid  Chemical Structure
  66. GC64508 γ-Aminobutyric acid-d6 γ-Aminobutyric acid-d6  Chemical Structure
  67. GC63279 γ-Glu-Gly TFA γ-Glu-Gly TFA  Chemical Structure
  68. GC63280 γ-Hexalactone γ-Hexalactone  Chemical Structure
  69. GC45238 δ14-Triamcinolone acetonide δ14-Triamcinolone acetonide is a potential impurity found in commercial preparations of triamcinolone acetonide. δ14-Triamcinolone acetonide  Chemical Structure
  70. GC45239 δ4-Abiraterone δ4-Abiraterone (D4A) is an active metabolite of the CYP17A1 inhibitor abiraterone. δ4-Abiraterone  Chemical Structure
  71. GC62708 σ1 Receptor antagonist-1 σ1 Receptor antagonist-1  Chemical Structure
  72. GC62067 ω-Conotoxin GVIA TFA ω-Conotoxin GVIA TFA  Chemical Structure
  73. GA24016 ω-Conotoxin MVIIA ω-Conotoxin MVIIA, originally isolated from the venom of the fish-hunting cone snail Conus magus, is a blocker of voltage-sensitive Ca²? channels in neurons. The peptide has been used to identify different Ca²? channel subtypes in amphibian brain. ω-Conotoxin MVIIA  Chemical Structure
  74. GC64899 ω-Conotoxin MVIIC TFA ω-Conotoxin MVIIC TFA  Chemical Structure
  75. GC63281 ω-Pentadecalactone ω-Pentadecalactone  Chemical Structure
  76. GC45713 (±)-α-Tocopherol Acetate (±)-α-Tocopherol Acetate  Chemical Structure
  77. GC52010 (±)-10-hydroxy-12(Z),15(Z)-Octadecadienoic Acid An oxylipin gut microbiota metabolite (±)-10-hydroxy-12(Z),15(Z)-Octadecadienoic Acid  Chemical Structure
  78. GC52013 (±)-10-hydroxy-12(Z)-Octadecenoic Acid An oxylipin and metabolite of linoleic acid (±)-10-hydroxy-12(Z)-Octadecenoic Acid  Chemical Structure
  79. GC38194 (±)-10-Hydroxycamptothecin (±)-10-Hydroxycamptothecin  Chemical Structure
  80. GC62726 (±)-Amiflamine (±)-Amiflamine  Chemical Structure
  81. GC34961 (±)-BI-D (±)-BI-D  Chemical Structure
  82. GC60394 (±)-Duloxetine hydrochloride (±)-Duloxetine hydrochloride  Chemical Structure
  83. GC49515 (±)-Ibuprofen-d3 (sodium salt) An internal standard for the quantification of (±)-ibuprofen (±)-Ibuprofen-d3 (sodium salt)  Chemical Structure
  84. GC45985 (±)-Indoxacarb (±)-Indoxacarb  Chemical Structure
  85. GC45278 (±)-Ketoprofen-d3   (±)-Ketoprofen-d3  Chemical Structure
  86. GC38369 (±)-Leucine (±)-Leucine  Chemical Structure
  87. GC65599 (±)-Leucine-d10 (±)-Leucine-d10  Chemical Structure
  88. GC45968 (±)-Liquiritigenin (±)-Liquiritigenin  Chemical Structure
  89. GC50708 (±)-ML 209 (±)-ML 209  Chemical Structure
  90. GC39271 (±)-Naringenin (±)-Naringenin  Chemical Structure
  91. GC49482 (±)-Nornicotine-d4 An internal standard for the quantification of (±)-nornicotine (±)-Nornicotine-d4  Chemical Structure
  92. GC62727 (±)-Penbutolol-d9 hydrochloride (±)-Penbutolol-d9 hydrochloride  Chemical Structure
  93. GC46008 (±)-Thalidomide-d4 (±)-Thalidomide-d4  Chemical Structure
  94. GC45618 (±)-trans-GK563 (±)-trans-GK563  Chemical Structure
  95. GC64007 (±)-U-50488 hydrate hydrochloride (±)-U-50488 hydrate hydrochloride  Chemical Structure
  96. GC45269 (±)10(11)-DiHDPA (±)10(11)-DiHDPA is produced from cytochrome P450 epoxygenase action on docosahexaenoic acid. (±)10(11)-DiHDPA  Chemical Structure
  97. GC45270 (±)10(11)-EDP Ethanolamide (±)10(11)-EDP ethanolamide is an ω-3 endocannabinoid epoxide and cannabinoid (CB) receptor agonist (EC50s = 0.43 and 22.5 nM for CB1 and CB2 receptors, respectively). (±)10(11)-EDP Ethanolamide  Chemical Structure
  98. GC46000 (•)-Drimenol (•)-Drimenol  Chemical Structure
  99. GA20003 ((R)-4-Hydroxy-4-methyl-Orn(FITC)⁷)-Phalloidin Fluorophore-labeled phalloidin used for visualizing the actin cytoskeleton. ((R)-4-Hydroxy-4-methyl-Orn(FITC)⁷)-Phalloidin  Chemical Structure
  100. GC45890 (+)-Abscisic Acid-d6 (+)-Abscisic Acid-d6  Chemical Structure
  101. GC39795 (+)-Afzelechin (+)-Afzelechin  Chemical Structure

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