NPASS Compound

Structure

CID222665 OpenBabel06191716012D 47 52 0 0 1 0 0 0 0 0999 V2000 3.0976 3.2452 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5033 -3.4360 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9997 -2.8523 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0093 1.5276 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8766 0.9366 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8799 0.0004 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0642 1.4018 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0708 -0.4705 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2552 0.9309 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6599 1.0503 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2198 0.5435 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9525 1.9509 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5124 1.4441 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4413 -1.4315 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6405 -0.0217 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6959 2.5889 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3598 3.0822 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2585 -0.0053 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2935 0.3466 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8788 2.1478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4478 -0.4954 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5863 3.0947 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6273 -1.8938 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8265 -0.4840 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4694 2.5765 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6470 -1.8832 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6404 -0.9471 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8199 -1.4201 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8205 -2.3672 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4577 -2.3512 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2358 1.5400 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3454 1.0343 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0002 -1.8936 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8201 -0.4735 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1873 3.1072 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5935 4.1186 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8235 -3.3492 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1684 -3.2415 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4908 -2.7440 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1714 3.0484 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6201 -2.9178 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3733 -2.1566 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1190 1.0218 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2430 2.5640 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3382 0.0103 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4622 1.5525 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 40 1 0 0 0 0 2 41 1 0 0 0 0 3 42 1 0 0 0 0 4 43 1 0 0 0 0 5 6 2 0 0 0 0 5 7 1 0 0 0 0 6 8 1 0 0 0 0 7 9 2 0 0 0 0 8 18 2 0 0 0 0 9 18 1 0 0 0 0 10 12 1 0 0 0 0 10 19 2 0 0 0 0 11 13 2 0 0 0 0 11 19 1 0 0 0 0 12 20 2 0 0 0 0 13 20 1 0 0 0 0 14 21 2 0 0 0 0 14 23 1 0 0 0 0 15 21 1 0 0 0 0 15 24 2 0 0 0 0 16 22 1 0 0 0 0 16 35 1 0 0 0 0 17 25 1 0 0 0 0 17 44 1 0 0 0 0 18 27 1 0 0 0 0 20 40 1 0 0 0 0 21 45 1 0 0 0 0 22 36 1 6 0 0 0 23 28 2 0 0 0 0 23 41 1 0 0 0 0 24 28 1 0 0 0 0 24 47 1 0 0 0 0 25 22 1 6 0 0 0 25 46 1 0 0 0 0 26 27 1 0 0 0 0 26 29 1 0 0 0 0 26 30 1 1 0 0 0 27 34 1 6 0 0 0 28 33 1 0 0 0 0 29 33 1 1 0 0 0 29 37 1 0 0 0 0 30 38 2 0 0 0 0 30 42 1 0 0 0 0 31 32 1 0 0 0 0 31 43 1 1 0 0 0 31 44 1 0 0 0 0 32 45 1 1 0 0 0 32 46 1 0 0 0 0 33 34 1 6 0 0 0 33 39 1 0 0 0 0 34 19 1 6 0 0 0 34 47 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	654.23
Volume:	633.19
LogP:	2.361
LogD:	2.335
LogS:	-4.447
# Rotatable Bonds:	11
TPSA:	171.83
# H-Bond Aceptor:	13
# H-Bond Donor:	4
# Rings:	6
# Heavy Atoms:	13

MedChem Properties

QED Drug-Likeness Score:	0.233
Synthetic Accessibility Score:	4.954
Fsp3:	0.441
Lipinski Rule-of-5:	Rejected
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:	-5.868
MDCK Permeability:	3.691221718327142e-05
Pgp-inhibitor:	0.989
Pgp-substrate:	0.956
Human Intestinal Absorption (HIA):	0.017
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.8

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.079
Plasma Protein Binding (PPB):	78.7203598022461%
Volume Distribution (VD):	0.445
Pgp-substrate:	11.173742294311523%

ADMET: Metabolism

CYP1A2-inhibitor:	0.006
CYP1A2-substrate:	0.237
CYP2C19-inhibitor:	0.024
CYP2C19-substrate:	0.737
CYP2C9-inhibitor:	0.039
CYP2C9-substrate:	0.051
CYP2D6-inhibitor:	0.006
CYP2D6-substrate:	0.403
CYP3A4-inhibitor:	0.806
CYP3A4-substrate:	0.73

ADMET: Excretion

Clearance (CL):	6.328
Half-life (T1/2):	0.168

ADMET: Toxicity

hERG Blockers:	0.41
Human Hepatotoxicity (H-HT):	0.609
Drug-inuced Liver Injury (DILI):	0.838
AMES Toxicity:	0.806
Rat Oral Acute Toxicity:	0.097
Maximum Recommended Daily Dose:	0.408
Skin Sensitization:	0.053
Carcinogencity:	0.849
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.079

Download Data

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

Natural Product: NPC222665

Natural Product ID:	NPC222665
*Common Name:**	5'''-Episilvestrol
IUPAC Name:	methyl (1R,2R,3S,3aR,8bS)-6-[[(2S,3S,6R)-6-[(1R)-1,2-dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate
Synonyms:	5'-Episilvestrol
Standard InCHIKey:	GVKXFVCXBFGBCD-GTDORJALSA-N
Standard InCHI:	InChI=1S/C34H38O13/c1-40-20-12-10-19(11-13-20)34-27(18-8-6-5-7-9-18)26(30(38)42-3)29(37)33(34,39)28-23(41-2)14-21(15-24(28)47-34)45-32-31(43-4)44-17-25(46-32)22(36)16-35/h5-15,22,25-27,29,31-32,35-37,39H,16-17H2,1-4H3/t22-,25-,26-,27-,29-,31+,32-,33+,34+/m1/s1
SMILES:	COc1ccc(cc1)[C@]12[C@H](c3ccccc3)[C@H]([C@H]([C@]1(c1c(cc(cc1O2)O[C@H]1[C@@H](OC)OC[C@H]([C@@H](CO)O)O1)OC)O)O)C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1651030
PubChem CID:	11679084
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000301] Benzofurans [CHEMONTID:0003109] Flavaglines

*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
NPO8087	Aglaia foveolata	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22817615]
NPO8087	Aglaia foveolata	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20939540]
NPO8087	Aglaia foveolata	Species	Meliaceae	Eukaryota	n.a.	stem	n.a.	PMID[20939540]
NPO8087	Aglaia foveolata	Species	Meliaceae	Eukaryota	n.a.	twig	n.a.	PMID[20939540]
NPO8087	Aglaia foveolata	Species	Meliaceae	Eukaryota	n.a.	fruit	n.a.	PMID[20939540]
NPO8087	Aglaia foveolata	Species	Meliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[20939540]
NPO8087	Aglaia foveolata	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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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
ED50	3
IC50	1

Activity Type	# Activity
Cell Line	1
Individual Protein	1
NON-MOLECULAR	2

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Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	ED50	=	1.5	nM	PMID[553279]
NPT139	Cell Line	HT-29	Homo sapiens	ED50	=	2.29	uM	PMID[553278]
NPT721	Individual Protein	Nuclear factor NF-kappa-B p65 subunit	Homo sapiens	IC50	>	20000.0	nM	PMID[553278]

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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 NPC222665 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	360
0.1-0.2	1392
0.2-0.3	3048
0.3-0.4	6233
0.4-0.5	10479
0.5-0.6	7668
0.6-0.7	7274
0.7-0.8	5954
0.8-0.85	270
0.85-0.9	4
0.9-0.95	11
0.95-1	4

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Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC271755
1.0	High Similarity	NPC149502
1.0	High Similarity	NPC254071
0.9437	High Similarity	NPC73422
0.9437	High Similarity	NPC310399

Showing 1 to 5 of 200 entries

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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 NPC222665 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	303
0.1-0.2	806
0.2-0.3	1822
0.3-0.4	2618
0.4-0.5	2130
0.5-0.6	1021
0.6-0.7	343
0.7-0.8	102
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	0

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Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8571	High Similarity	NPD7199	Phase 2
0.8363	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.8176	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.8136	Intermediate Similarity	NPD7685	Pre-registration
0.8114	Intermediate Similarity	NPD7228	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