NPASS Compound

Structure

CID137705 OpenBabel06191715492D 29 29 0 0 1 0 0 0 0 0999 V2000 -3.4543 0.6389 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9010 6.8679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9680 -0.6994 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8795 3.8823 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 1.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8090 0.5878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9895 2.2862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3658 5.2206 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1974 1.3080 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1089 5.8897 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7601 0.2788 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0385 2.5952 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5737 4.2425 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2953 1.9260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8090 0.5878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1485 0.9990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0600 5.5807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8176 0.2559 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -4.8395 0.0479 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -5.8916 1.6681 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -5.7291 4.8376 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -4.7510 4.6297 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -5.8031 6.2498 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 1.5388 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5032 0.9479 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.8305 3.5733 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.5247 3.9334 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3443 2.2351 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 4 26 1 0 0 0 0 5 6 2 0 0 0 0 5 24 1 0 0 0 0 6 29 1 0 0 0 0 7 9 1 0 0 0 0 8 10 1 0 0 0 0 8 13 1 0 0 0 0 9 1 1 6 0 0 0 9 16 1 0 0 0 0 10 2 1 1 0 0 0 10 17 1 0 0 0 0 11 3 1 6 0 0 0 11 15 1 0 0 0 0 11 25 1 0 0 0 0 12 7 1 6 0 0 0 12 14 1 0 0 0 0 12 26 1 0 0 0 0 13 26 1 0 0 0 0 13 27 2 0 0 0 0 14 25 2 3 0 0 0 14 28 1 0 0 0 0 15 24 2 0 0 0 0 15 29 1 0 0 0 0 16 18 1 0 0 0 0 16 19 1 0 0 0 0 16 20 1 0 0 0 0 17 21 1 0 0 0 0 17 22 1 0 0 0 0 17 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	542.96
Volume:	443.832
LogP:	4.311
LogD:	3.058
LogS:	-4.638
# Rotatable Bonds:	12
TPSA:	62.3
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	1
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.411
Synthetic Accessibility Score:	4.378
Fsp3:	0.706
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.643
MDCK Permeability:	0.00016341893933713436
Pgp-inhibitor:	0.011
Pgp-substrate:	0.032
Human Intestinal Absorption (HIA):	0.011
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.001

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.99
Plasma Protein Binding (PPB):	94.39866638183594%
Volume Distribution (VD):	1.088
Pgp-substrate:	2.191876173019409%

ADMET: Metabolism

CYP1A2-inhibitor:	0.038
CYP1A2-substrate:	0.537
CYP2C19-inhibitor:	0.837
CYP2C19-substrate:	0.904
CYP2C9-inhibitor:	0.146
CYP2C9-substrate:	0.084
CYP2D6-inhibitor:	0.004
CYP2D6-substrate:	0.293
CYP3A4-inhibitor:	0.944
CYP3A4-substrate:	0.941

ADMET: Excretion

Clearance (CL):	4.259
Half-life (T1/2):	0.114

ADMET: Toxicity

hERG Blockers:	0.017
Human Hepatotoxicity (H-HT):	0.849
Drug-inuced Liver Injury (DILI):	0.189
AMES Toxicity:	0.169
Rat Oral Acute Toxicity:	0.03
Maximum Recommended Daily Dose:	0.833
Skin Sensitization:	0.074
Carcinogencity:	0.118
Eye Corrosion:	0.003
Eye Irritation:	0.01
Respiratory Toxicity:	0.971

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC137705

Natural Product ID:	NPC137705
*Common Name:**	Dysidenin
IUPAC Name:	(2S,4S)-5,5,5-trichloro-4-methyl-2-[methyl-[(3S)-4,4,4-trichloro-3-methylbutanoyl]amino]-N-[(1S)-1-(1,3-thiazol-2-yl)ethyl]pentanamide
Synonyms:	Dysidenin
Standard InCHIKey:	BFVRAKVNXYQMID-BJDJZHNGSA-N
Standard InCHI:	InChI=1S/C17H23Cl6N3O2S/c1-9(16(18,19)20)7-12(14(28)25-11(3)15-24-5-6-29-15)26(4)13(27)8-10(2)17(21,22)23/h5-6,9-12H,7-8H2,1-4H3,(H,25,28)/t9-,10-,11-,12-/m0/s1
SMILES:	OC(=N[C@H](c1nccs1)C)[C@@H](N(C(=O)C[C@@H](C(Cl)(Cl)Cl)C)C)C[C@@H](C(Cl)(Cl)Cl)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL391079
PubChem CID:	10007601
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO17673	Dysidea herbacea	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[10075800]
NPO17673	Dysidea herbacea	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[10650102]
NPO17673	Dysidea herbacea	Species	n.a.	n.a.	n.a.	Mandapam Coast, Tamilnadu, India	n.a.	PMID[22704923]
NPO17673	Dysidea herbacea	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[9463111]
NPO13746	Achillea leptophylla	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4863	Dioscorea futschauensis	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4863	Dioscorea futschauensis	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13746	Achillea leptophylla	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16323	Umbilicaria proboscidea	Species	Umbilicariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4863	Dioscorea futschauensis	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4863	Dioscorea futschauensis	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13746	Achillea leptophylla	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13321	Viguiera cordifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1793	Uvaria mocoli	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17210	Dorstenia barnimiana	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9044	Rubia ustulata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13985	Oxybasis urbica	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16204	Zieria chevalieri	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17991	Sedum forsterianum	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7857	Verbascum georgicum	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16323	Umbilicaria proboscidea	Species	Umbilicariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16684	Alibertia macrophylla	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17673	Dysidea herbacea	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO4863	Dioscorea futschauensis	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Ki	2
Others	1

Activity Type	# Activity
Individual Protein	2
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1119	Individual Protein	Arachidonate 12-lipoxygenase	Homo sapiens	Ki	=	9000.0	nM	PMID[508045]
NPT792	Individual Protein	Arachidonate 15-lipoxygenase	Homo sapiens	Ki	=	8000.0	nM	PMID[508045]
NPT2	Others	Unspecified		Ratio Ki	=	1.0	n.a.	PMID[508045]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC137705 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	264
0.1-0.2	32364
0.2-0.3	7199
0.3-0.4	2548
0.4-0.5	271
0.5-0.6	39
0.6-0.7	7
0.7-0.8	2
0.8-0.85	0
0.85-0.9	0
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9487	High Similarity	NPC145047
0.9487	High Similarity	NPC86490
0.7462	Intermediate Similarity	NPC278902
0.7388	Intermediate Similarity	NPC275393
0.6966	Remote Similarity	NPC478251
0.6966	Remote Similarity	NPC478252
0.6831	Remote Similarity	NPC478254
0.6831	Remote Similarity	NPC478253
0.6667	Remote Similarity	NPC261708
0.6575	Remote Similarity	NPC103268
0.6562	Remote Similarity	NPC475920
0.6424	Remote Similarity	NPC475390
0.614	Remote Similarity	NPC161143
0.5889	Remote Similarity	NPC239660
0.5889	Remote Similarity	NPC106235
0.5887	Remote Similarity	NPC214375
0.5808	Remote Similarity	NPC475554
0.5804	Remote Similarity	NPC135558
0.5793	Remote Similarity	NPC267605
0.5743	Remote Similarity	NPC89592
0.5706	Remote Similarity	NPC164006
0.5685	Remote Similarity	NPC51692

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC137705 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	105
0.1-0.2	2148
0.2-0.3	4488
0.3-0.4	2144
0.4-0.5	256
0.5-0.6	9
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5889	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5833	Remote Similarity	NPD222	Approved
0.5685	Remote Similarity	NPD2225	Clinical (unspecified phase)
0.5625	Remote Similarity	NPD221	Approved

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data