NPASS Compound

Structure

CID310341 OpenBabel06191716122D 38 43 0 0 1 0 0 0 0 0999 V2000 6.1493 1.2712 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5503 0.5272 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0006 1.9983 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1532 -0.5973 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7009 -1.9628 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8506 -1.4722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2498 -0.4896 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7000 0.9815 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6994 0.9806 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4001 0.0010 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8497 1.4721 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6991 -0.0005 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3608 3.3017 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4006 -1.9623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8101 2.6559 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3535 0.3115 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8509 2.4523 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5509 -1.4717 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2500 -1.4713 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8506 1.4716 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7003 0.0005 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8503 -0.4906 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0172 4.0302 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2868 0.0086 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7621 -1.6078 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.4910 -0.9511 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8288 -1.3049 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5506 -0.4901 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0003 0.9810 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8136 4.9895 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0157 0.6653 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9663 -2.5674 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0003 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4242 -1.2540 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9129 3.6311 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6246 -0.3452 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0999 -1.9616 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3 29 1 0 0 0 0 4 35 1 0 0 0 0 5 6 1 0 0 0 0 5 18 1 0 0 0 0 6 22 1 0 0 0 0 7 10 1 0 0 0 0 7 19 1 0 0 0 0 8 11 1 0 0 0 0 8 21 1 0 0 0 0 9 12 1 0 0 0 0 9 20 1 0 0 0 0 10 28 1 0 0 0 0 11 29 1 0 0 0 0 12 30 1 0 0 0 0 13 17 2 0 0 0 0 13 23 1 0 0 0 0 14 18 1 0 0 0 0 14 19 1 0 0 0 0 15 17 1 0 0 0 0 15 36 1 0 0 0 0 16 1 1 1 0 0 0 16 24 1 0 0 0 0 16 37 1 0 0 0 0 17 20 1 0 0 0 0 18 28 1 6 0 0 0 19 38 1 6 0 0 0 20 29 1 6 0 0 0 21 22 1 0 0 0 0 21 28 1 6 0 0 0 22 30 1 1 0 0 0 23 31 2 0 0 0 0 23 36 1 0 0 0 0 24 26 1 0 0 0 0 24 32 1 6 0 0 0 25 26 1 0 0 0 0 25 27 1 0 0 0 0 25 33 1 6 0 0 0 26 35 1 1 0 0 0 27 37 1 0 0 0 0 27 38 1 6 0 0 0 28 2 1 6 0 0 0 29 30 1 6 0 0 0 30 34 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	534.32
Volume:	541.146
LogP:	3.937
LogD:	3.594
LogS:	-4.35
# Rotatable Bonds:	4
TPSA:	121.75
# H-Bond Aceptor:	8
# H-Bond Donor:	4
# Rings:	6
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.426
Synthetic Accessibility Score:	5.219
Fsp3:	0.867
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-5.251
MDCK Permeability:	2.1604617359116673e-05
Pgp-inhibitor:	0.81
Pgp-substrate:	0.996
Human Intestinal Absorption (HIA):	0.821
20% Bioavailability (F20%):	0.073
30% Bioavailability (F30%):	0.687

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.1
Plasma Protein Binding (PPB):	94.14810943603516%
Volume Distribution (VD):	1.093
Pgp-substrate:	4.726527690887451%

ADMET: Metabolism

CYP1A2-inhibitor:	0.018
CYP1A2-substrate:	0.846
CYP2C19-inhibitor:	0.009
CYP2C19-substrate:	0.48
CYP2C9-inhibitor:	0.082
CYP2C9-substrate:	0.05
CYP2D6-inhibitor:	0.012
CYP2D6-substrate:	0.207
CYP3A4-inhibitor:	0.411
CYP3A4-substrate:	0.203

ADMET: Excretion

Clearance (CL):	10.126
Half-life (T1/2):	0.266

ADMET: Toxicity

hERG Blockers:	0.619
Human Hepatotoxicity (H-HT):	0.319
Drug-inuced Liver Injury (DILI):	0.044
AMES Toxicity:	0.032
Rat Oral Acute Toxicity:	0.754
Maximum Recommended Daily Dose:	0.934
Skin Sensitization:	0.913
Carcinogencity:	0.583
Eye Corrosion:	0.003
Eye Irritation:	0.013
Respiratory Toxicity:	0.977

Download Data

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

Natural Product: NPC310341

Natural Product ID:	NPC310341
*Common Name:**	Thevefolin
IUPAC Name:	3-[(3S,5S,8R,9S,10S,13R,14S,17R)-3-[(2R,3S,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxy-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
Synonyms:	Thevefolin
Standard InCHIKey:	VPUNMTHWNSJUOG-WEFSHINVSA-N
Standard InCHI:	InChI=1S/C30H46O8/c1-16-24(32)26(35-4)25(33)27(37-16)38-19-7-10-28(2)18(14-19)5-6-22-21(28)8-11-29(3)20(9-12-30(22,29)34)17-13-23(31)36-15-17/h13,16,18-22,24-27,32-34H,5-12,14-15H2,1-4H3/t16-,18-,19-,20+,21-,22+,24-,25-,26+,27-,28-,29+,30-/m0/s1
SMILES:	CO[C@H]1[C@H](O)[C@H](O[C@H]2CC[C@]3([C@H](C2)CC[C@@H]2[C@@H]3CC[C@]3([C@]2(O)CC[C@@H]3C2=CC(=O)OC2)C)C)O[C@H]([C@@H]1O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1078503
PubChem CID:	44537896
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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

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Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO8402	Thevetia peruviana	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26714048]
NPO8402	Thevetia peruviana	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17609	Thevetia neriifolia	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17609	Thevetia neriifolia	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17609	Thevetia neriifolia	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]

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☑ 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

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Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference
No data available in table

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☑ 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
IC50	4
Others	8

Activity Type	# Activity
Cell Line	9
NON-MOLECULAR	2
Others	1

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Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1312	Cell Line	SW1990	Homo sapiens	IC50	=	30.0	nM	PMID[452645]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	10.0	nM	PMID[452645]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	370.0	nM	PMID[452645]
NPT27	Others	Unspecified	""	IC50	>	10000.0	nM	PMID[452645]
NPT196	Cell Line	AGS	Homo sapiens	Activity	=	46.0	%	PMID[452644]
NPT196	Cell Line	AGS	Homo sapiens	Activity	=	65.0	%	PMID[452644]
NPT196	Cell Line	AGS	Homo sapiens	FC	=	1.8	n.a.	PMID[452644]
NPT196	Cell Line	AGS	Homo sapiens	FC	=	3.3	n.a.	PMID[452644]
NPT196	Cell Line	AGS	Homo sapiens	FC	=	3.6	n.a.	PMID[452644]
NPT196	Cell Line	AGS	Homo sapiens	FC	=	1.2	n.a.	PMID[452644]

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☑ 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 NPC310341 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	244
0.1-0.2	1668
0.2-0.3	5066
0.3-0.4	11039
0.4-0.5	10082
0.5-0.6	6495
0.6-0.7	4599
0.7-0.8	2727
0.8-0.85	472
0.85-0.9	139
0.9-0.95	91
0.95-1	75

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Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC199428
1.0	High Similarity	NPC99620
1.0	High Similarity	NPC5311
1.0	High Similarity	NPC193382
0.9907	High Similarity	NPC196429

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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 NPC310341 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	212
0.1-0.2	1795
0.2-0.3	4072
0.3-0.4	2051
0.4-0.5	537
0.5-0.6	271
0.6-0.7	166
0.7-0.8	31
0.8-0.85	2
0.85-0.9	0
0.9-0.95	8
0.95-1	5

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Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9815	High Similarity	NPD7328	Approved
0.9815	High Similarity	NPD7327	Approved
0.9725	High Similarity	NPD7516	Approved
0.9636	High Similarity	NPD8294	Approved
0.9636	High Similarity	NPD8377	Approved

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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