Basic information

CPKB ID	CP00005
IUPAC Name	N-(1-amino-3-hydroxy-1-oxobutan-2-yl)-19-[(2-amino-3-phenylpropanoyl)amino]-10-(3-aminopropyl)-7-(1-hydroxyethyl)-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-3,3-dimethyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide
Synonyms	103429-31-8 C20160 Ctop Ctopa Ctop-Nh2 Fcywxtxt L000207 L-Threoninamide,-D-Phenylalanyl-L-Cysteinyl-L-Tyrosyl-D-Tryptophyl-L-Ornithyl-L-Threonyl-3-Mercapto-L-Valyl-,-Cyclic-(2-7)-Disulfide N-(1-Amino-3-Hydroxy-1-Oxobutan-2-Yl)-19-[(2-Amino-3-Phenylpropanoyl)Amino]-10-(3-Aminopropyl)-7-(1-Hydroxyethyl)-16-[(4-Hydroxyphenyl)Methyl]-13-(1H-Indol-3-Ylmethyl)-3,3-Dimethyl-6,9,12,15,18-Pentaoxo-1,2-Dithia-5,8,11,14,17-Pentazacycloicosane-4-Carboxamide Phenylalanyl-Cyclo(Cysteinyltyrosyl-Tryptophyl-Ornithyl-Threonyl-Penicillamine) Phenylalanyl-Cyclo(Cysteinyltyrosyl-Tryptophyl-Ornithyl-Threonyl-Penicillamine)Threoninamide Schembl1239661

Legend

Structure

Molecular Formula	C50H67N11O11S2
Molecular Weight	1061.446294 g/mol
SMILES RUN SEA Predictions	CC(O)C(NC(=O)C1NC(=O)C(C(C)O)NC(=O)C(CCCN)NC(=O)C(Cc2c[nH]c3ccccc23)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C(NC(=O)C(N)Cc2ccccc2)CSSC1(C)C)C(N)=O PubChem\|2884
InChI	InChI=1S/C50H67N11O11S2/c1-26(62)39(42(53)65)59-49(72)41-50(3,4)74-73-25-38(58-43(66)33(52)21-28-11-6-5-7-12-28)47(70)56-36(22-29-16-18-31(64)19-17-29)45(68)57-37(23-30-24-54-34-14-9-8-13-32(30)34)46(69)55-35(15-10-20-51)44(67)60-40(27(2)63)48(71)61-41/h5-9,11-14,16-19,24,26-27,33,35-41,54,62-64H,10,15,20-23,25,51-52H2,1-4H3,(H2,53,65)(H,55,69)(H,56,70)(H,57,68)(H,58,66)(H,59,72)(H,60,67)(H,61,71)
InChIKey	PZWWYAHWHHNCHO-LOWIJWPFNA-N

2D Structure PubChem\|2884

Sequence

IUPAC Condensed	H-DL-Phe-DL-Cys(1)-DL-Tyr-DL-Trp-DL-Orn-DL-xiThr-DL-Pen(1)-DL-xiThr-NH2 PubChem\|2884
Amino acid chain	H-DL-Phe--DL-Cys(1)--DL-Tyr--DL-Trp--DL-Orn--DL-xiThr--DL-Pen(1)--DL-xiThr-NH2 CyclicPepedia\|PP
Graph representation	H-DL-Phe,DL-Cys,DL-Tyr,DL-Trp,DL-Orn,DL-xiThr,DL-Pen,DL-xiThr-NH2 @1,6 CyclicPepedia\|PP
One letter code from Structure	FCYWATCT CyclicPepedia\|Struct2seq
Amino acid chain from Structure	Phe--Cys(1)--Tyr--Trp--Orn--Thr--Pen(1)--Eta CyclicPepedia\|Struct2seq
Description of the conversion sequence	The one letter code and Amino acid chain derived from the structural transformation may be inconsistent, with the Amino acid chain containing Essential Amino acid and the one letter code not.
svg Image PubChem\|2884

Chemical and Physical Properties

CyclicPepedia|Struc2Seq + PP

Structure Properties

Property Name	Property Value
Exact Mass	1061.446294
Number of Rings	5.0
Complexity	0.77027027
XlogP3 AA	-1.2183
Heavy Atom Count	74.0
Hydrogen Bond Donor Count	14.0
Hydrogen Bond Acceptor Count	15.0
Rotatable Bond Count	16.0

Property Name	Property Value
Formal Charge	0.0
Refractivity	280.4222
Rule_of_Five	0.0
Number of Atoms	74.0
Topological Polar Surface Area	375.31
Refractivity	280.4222
Veber Rule	0.0
Ghose Filter	0.0

Property Name	Property Value
RDKit Fingerprint	11000111110100101111110011110000111101100111100000011011101001101110101110111111111111010100110011110101110101001010011001110111010001011000111100001111000010010101001100111111101111001111000101110100111001001000000110000001010001000101010110001110011101111111010111101110000111101111110000000010000011011111100111010001110100000011111110110110011100000010111100001001100001000010101001101010010100000110000100001110000010110001101000111011110000100000110000010110111000011100000100001110001101000111100100101111111101111110110110001101101010101101100001010110101001100110010010001001000110111100101110010001101010011010100000111111110100111100100111110111011001001110111110111111010111001001011100110001101101101000000111011010101101001111101010110010001110101011100110011000001111001101011010111011001010011011101000001101111011110000011011111101111001110111011100110011010110000111001010000011101101100110111110110110011101110010110001011101101010011011111100110000011001010110001001110011110101000001000000111101111111110111110110111111110101001011000101001110111101100001100001001001110110000111001101001010000011101001100010101101110010010110101000011010101010110100101111001001010011111110011011001000100101011101110011100100011101110111011010011001101111000110101110001010100101111000110100011001011010111101100111110111111001001011111111010000011110110011110010110001111101011111001101000111100101001100100011110101101011001000011001111100100101001011101110101110010101110001110000111111001011010001110100100111111011100101011000010100011111110100110101100000100111100101001011010111000010000011101111101011011010100001010110100010100001100010010010001011001111000110101111100100000010110001111110100100100101000101010110111100100010100011011001011101111010010111100110001000110001111111100011110011111111101100100101110010111110100111111011000001101001110000011011101010010100001101101110010100111111000111011011010111001110010111110110100011111001011101011001001011101101100111010101111100110110011000001011101100010100100100101001111011
Morgan Fingerprint	0101000000100000000000000000000001001000001000000000000000000000100000000000000110000000001000100000000000000000000101010000010010000000000010000001000000000000100000000000000100000000000010000000000000000000000000000000100000010000000000000000100010100000000000000000000000000000001100000100000000000100000000100010000000000100100001000000000000000000000110000000100000000000000000000001010000000000000000000000000000000000000000001001000000000000000000000010000000000000001000100010000000001100000000000000010000000001100000000000000000000000000001000000000010000000000001000010000100000000000000000000000000000000000000000000000000000000000000000010000000000000010001000001000000000001010000000000000000000001000100000000001000100000000000000100000000100001000000000000000000000000001000000000000000001011000010001000100001000000110000000000000001001001010000000100000000000000000000010000010000000000000000000100010000000010000000000000010000000000000001100000001000000000100001000000000000000000000000100100000001010000
MACCS Keys	00000000000000100000000000000000000010000000000000000110000000000111000000100001011110001111100111001100110010111100011011001101000101001111111101110111111111111111110

Sequence Properties

Property Name	Property Value
Boman Index	-0.55
Instability	17.75
Charge	-0.126815546676281
Aliphatic Index	12.5

Binding Target

Detail

Uniprot: P41143

Kind: Protein>

Organism: Homo sapiens(Human)

Evidevce: TTD

Sequence: MEPAPSAGAELQPPLFANASDAYPSACPSAGANASGPPGARSASSLALAIAITALYSAVCAVGLLGNVLVMFGIVRYTKMKTATNIYIFNLALADALATSTLPFQSAKYLMETWPFGELLCKAVLSIDYYNMFTSIFTLTMMSVDRYIAVCHPVKALDFRTPAKAKLINICIWVLASGVGVPIMVMAVTRPRDGAVVCMLQFPSPSWYWDTVTKICVFLFAFVVPILIITVCYGLMLLRLRSVRLLSGSKEKDRSLRRITRMVLVVVGAFVVCWAPIHIFVIVWTLVDIDRRDPLVVAALHLCIALGYANSSLNPVLYAFLDENFKRCFRQLCRKPCGRPDPSSFSRAREATARERVTACTPSDGPGGGAAA

General Function:

G-protein coupled receptor

Specific Function:

G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.

Additional database information: TTD[Opioid receptor delta (oprd1)]

Detail

Uniprot: P35372

Kind: Protein>

Organism: Homo sapiens(Human)

Evidevce: TTD

Sequence: MDSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDPCGPNRTDLGGRDSLCPPTGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALATSTLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDFRTPRNAKIINVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFIFAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHIYVIIKALVTIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNIEQQNSTRIRQNTRDHPSTANTVDRTNHQLENLEAETAPLP

General Function:

G-protein coupled receptor

Specific Function:

Receptor for endogenous opioids such as beta-endorphin and endomorphin

Additional database information: TTD[Opioid receptor mu (mop)]

Other evidence

Property Name	Property ID
TTD	D0MZ2A
DrugMAP	DM7VAJX

Manufacturers

Manufacturers Name	Value
CreativePeptides	Ctopa
Bayer healthcare pharmaceuticals	Ctopa
Upsher smith laboratories	Ctopa
Merck	Ctopa

Manufacturers Name	Value
Apotex	Ctopa
Baxter Healthcare Corp	Ctopa
Pharmasources	Ctopa
Novartis	Ctopa
AstraZeneca	Ctopa

Forecasting tools

Forecasting tools	Value
Structure to Sequence	CC(O)C(NC(=O)C1NC(=O)C(C(C)O)NC(=O)C(CCCN)NC(=O)C(Cc2c[nH]c3ccccc23)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C(NC(=O)C(N)Cc2ccccc2)CSSC1(C)C)C(N)=O
Structure Properties	CC(O)C(NC(=O)C1NC(=O)C(C(C)O)NC(=O)C(CCCN)NC(=O)C(Cc2c[nH]c3ccccc23)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C(NC(=O)C(N)Cc2ccccc2)CSSC1(C)C)C(N)=O
Sequence to Structure	FCYWATCT
Sequence Properties	FCYWATCT
Expasy ProtParam Tool	FCYWATCT
SEA	RUN SEA Predictions

Information Source

Property Name	Property ID
Patents	PZWWYAHWHHNCHO-LOWIJWPFNA-N
pubchem	2884
Drugbank	Ctopa
DRAMP3	Ctopa
Uniprot	Ctopa
Cybase	Ctopa
CONOSERVER	Ctopa
BindingDB	CC(O)C(NC(=O)C1NC(=O)C(C(C)O)NC(=O)C(CCCN)NC(=O)C(Cc2c[nH]c3ccccc23)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C(NC(=O)C(N)Cc2ccccc2)CSSC1(C)C)C(N)=O
CHEMBL	Ctopa
CTD	C049352
Wikipedia	Ctopa
KEGG Compound/Drug	Ctopa
CHEBI	PZWWYAHWHHNCHO-LOWIJWPFNA-N
EPA DSSTox	Ctopa
FDA Global Substance Registration System (GSRS)	Ctopa
DTP/NCI	Ctopa
Chemspider	PZWWYAHWHHNCHO-LOWIJWPFNA-N

Reference

Pubmed_ID	Title	DOI	Journal
2872570	Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors	10.1016/0024-3205(86)90574-6.	Life Sci
Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors Abstract A series of cyclic conformationally restricted penicillamine containing somatostatin octapeptide analogues have been prepared by standard solid phase synthetic techniques and tested for their ability to inhibit specific 125ICGP 23,996 (des-Ala1-,Gly2-desamino-Cys3Tyr11-dicarba3, 14-somatostatin), 3Hnaloxone or 3HDPDPE (D-Pen2-D-Pen5enkephalin) binding in rat brain membrane preparations. We now report structure-activity relationship studies with the synthesis of our most potent and selective mu opioid receptor compound D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, which we refer to as Cys2Tyr3Orn5Pen7-amide. While this octapeptide exhibited high affinity (IC50 = 2.80 nM) for an apparently single population of binding sites (nH = 0.89 +/- 0.1) and exceptional selectivity for mu opioid receptors with an IC50(DPDPE)/IC50 (naloxone) ratio of 4,829, it also displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM). Thus, Cys2Tyr3Orn5Pen7-amide may be the ligand of choice for further characterization of mu opioid receptors and for examining the physiological role of this class of receptors.
2893264	H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors	None	NIDA Res Monogr
H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors Abstract H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) exhibited high affinity (IC50 = 2.80 nM) in displacing 3Hnaloxone binding (nH = 0.89 +/- 0.1) and showed an exceptional selectivity for mu opioid receptors with an IC50(DPDPE)/IC50(naloxone) ratio of 4,840, while it displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM) in rat brain binding assays. 3HCTOP was recently custom synthesized (spec. act.: 84 Ci/mmol) and evaluated for its in vitro binding properties towards the mu opioid receptors in rat brain membrane preparations. Association and dissociation of 3HCTOP binding to mu opioid receptors were rapid at 25 degrees C with a kinetic Kd value of 0.67 nM. Saturation experiments gave apparent Kd value of 1.11 nM and Bmax value of 136 +/- 13 fmol/mg prot at 25 degrees C. Specific 3HCTOP binding was inhibited by a number of different opioid and opiate ligands. Among them, putative mu opioid receptor-specific ligands, such as naloxone, naltrexone and CTOP inhibited the binding with high affinity, while delta opioid receptor-specific compounds or non-opioid drugs inhibited specific 3HCTOP binding with low affinity or they were ineffective.

Ctopa

Basic information

Legend

Structure

Download structure

Sequence

Chemical and Physical Properties

Structure Properties

Sequence Properties

Binding Target

Opioid receptor delta (oprd1)

Detail

Uniprot: P41143

Kind: Protein>

Organism: Homo sapiens(Human)

Evidevce: TTD

General Function:

Specific Function:

Additional database information: TTD[Opioid receptor delta (oprd1)]

Opioid receptor mu (mop)

Detail

Uniprot: P35372

Kind: Protein>

Organism: Homo sapiens(Human)

Evidevce: TTD

General Function:

Specific Function:

Additional database information: TTD[Opioid receptor mu (mop)]

Other evidence

Manufacturers

Forecasting tools

Information Source

Reference

Cyclic somatostatin octapeptide analogues with high affinity and selectivity toward mu opioid receptors

Abstract

H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors

Abstract