NPASS Compound

Structure

CID73422 OpenBabel06191715412D 36 40 0 0 1 0 0 0 0 0999 V2000 -3.1451 -3.2489 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3645 -1.0662 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5474 3.4454 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0111 2.9031 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9217 -0.9094 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9184 0.0341 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1063 -1.3840 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0996 0.5030 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2875 -0.9151 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6726 -1.0539 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2411 -0.5320 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9739 -1.9595 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5425 -1.4377 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4707 1.4255 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6536 0.0102 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2842 0.0284 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3062 -0.3402 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9088 -2.1514 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4707 0.4820 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6536 1.8973 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8364 0.4820 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6466 1.9097 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6466 0.9662 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8364 1.4255 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8102 2.3917 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4604 2.3872 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0133 1.9085 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8232 0.4830 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8063 3.3681 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1625 3.2825 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5074 2.7507 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2101 -3.0570 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3645 -0.0341 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6536 2.9294 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3847 2.1975 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 32 1 0 0 0 0 2 33 1 0 0 0 0 3 34 1 0 0 0 0 4 35 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 16 2 0 0 0 0 9 16 1 0 0 0 0 10 12 1 0 0 0 0 10 17 2 0 0 0 0 11 13 2 0 0 0 0 11 17 1 0 0 0 0 12 18 2 0 0 0 0 13 18 1 0 0 0 0 14 19 2 0 0 0 0 14 20 1 0 0 0 0 15 19 1 0 0 0 0 15 21 2 0 0 0 0 16 23 1 0 0 0 0 18 32 1 0 0 0 0 19 33 1 0 0 0 0 20 24 2 0 0 0 0 20 34 1 0 0 0 0 21 24 1 0 0 0 0 21 36 1 0 0 0 0 22 23 1 0 0 0 0 22 25 1 0 0 0 0 22 26 1 1 0 0 0 23 28 1 6 0 0 0 24 27 1 0 0 0 0 25 27 1 1 0 0 0 25 29 1 0 0 0 0 26 30 2 0 0 0 0 26 35 1 0 0 0 0 27 28 1 6 0 0 0 27 31 1 0 0 0 0 28 17 1 6 0 0 0 28 36 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	492.18
Volume:	494.019
LogP:	3.52
LogD:	3.319
LogS:	-4.884
# Rotatable Bonds:	7
TPSA:	103.68
# H-Bond Aceptor:	8
# H-Bond Donor:	2
# Rings:	5
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.506
Synthetic Accessibility Score:	3.915
Fsp3:	0.321
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.287
MDCK Permeability:	5.2914725529262796e-05
Pgp-inhibitor:	0.992
Pgp-substrate:	0.017
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.056
30% Bioavailability (F30%):	0.796

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.673
Plasma Protein Binding (PPB):	85.04096984863281%
Volume Distribution (VD):	1.444
Pgp-substrate:	8.774401664733887%

ADMET: Metabolism

CYP1A2-inhibitor:	0.055
CYP1A2-substrate:	0.768
CYP2C19-inhibitor:	0.756
CYP2C19-substrate:	0.818
CYP2C9-inhibitor:	0.722
CYP2C9-substrate:	0.511
CYP2D6-inhibitor:	0.101
CYP2D6-substrate:	0.901
CYP3A4-inhibitor:	0.957
CYP3A4-substrate:	0.887

ADMET: Excretion

Clearance (CL):	9.29
Half-life (T1/2):	0.17

ADMET: Toxicity

hERG Blockers:	0.418
Human Hepatotoxicity (H-HT):	0.551
Drug-inuced Liver Injury (DILI):	0.622
AMES Toxicity:	0.35
Rat Oral Acute Toxicity:	0.344
Maximum Recommended Daily Dose:	0.675
Skin Sensitization:	0.029
Carcinogencity:	0.101
Eye Corrosion:	0.003
Eye Irritation:	0.014
Respiratory Toxicity:	0.728

Download Data

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

Natural Product: NPC73422

Natural Product ID:	NPC73422
*Common Name:**	Aglafolin
IUPAC Name:	methyl (1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate
Synonyms:	Aglafolin; Methyl Rocaglate
Standard InCHIKey:	VFTGDXPPYSWBSO-GWNOIRNCSA-N
Standard InCHI:	InChI=1S/C28H28O8/c1-32-18-12-10-17(11-13-18)28-23(16-8-6-5-7-9-16)22(26(30)35-4)25(29)27(28,31)24-20(34-3)14-19(33-2)15-21(24)36-28/h5-15,22-23,25,29,31H,1-4H3/t22-,23-,25-,27+,28+/m1/s1
SMILES:	COc1ccc(cc1)[C@]12[C@H](c3ccccc3)[C@H]([C@H]([C@]1(c1c(cc(cc1O2)OC)OC)O)O)C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL394528
PubChem CID:	393601
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
NPO32616	aglaia sp.	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9868148]
NPO10244	Aglaia elliptifolia	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9214732]
NPO27686	Aglaia odorata	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8759160]
NPO32616	aglaia sp.	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8496701]
NPO4720	Aglaia perviridis	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31621322]
NPO4720	Aglaia perviridis	Species	Meliaceae	Eukaryota	leaves, twigs, and fruits	Nui Chua National Park (11 43' N; 109 08' E; 730 m alt.), Ninh Thuan Province, Vietnam	2010-Jan	PMID[23301897]
NPO27686	Aglaia odorata	Species	Meliaceae	Eukaryota	n.a.	flower	n.a.	PMID[17679444]
NPO3427	Aglaia rubiginosa	Species	Meliaceae	Eukaryota	twigs and leaves	n.a.	n.a.	PMID[15043407]
NPO10244	Aglaia elliptifolia	Species	Meliaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[11170675]
NPO32616	aglaia sp.	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10775404]

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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
EC50	6
ED50	9
IC50	7
MIC	3
Others	8

Activity Type	# Activity
Cell Line	13
Individual Protein	4
NON-MOLECULAR	5
Organism	9
Others	2

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Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell Line	HT-29	Homo sapiens	ED50	=	0.012	uM	PMID[544200]
NPT27	Others	Unspecified		ED50	>	50.0	uM	PMID[544200]
NPT721	Individual Protein	Nuclear factor NF-kappa-B p65 subunit	Homo sapiens	ED50	>	20.0	uM	PMID[544200]
NPT3821	Organism	Alternaria citri	Alternaria citri	MIC	=	200.0	ug.mL-1	PMID[544199]
NPT3821	Organism	Alternaria citri	Alternaria citri	EC90	=	171.0	ug ml-1	PMID[544199]
NPT3660	Organism	Fusarium avenaceum	Fusarium avenaceum	MIC	=	100.0	ug.mL-1	PMID[544199]
NPT3660	Organism	Fusarium avenaceum	Fusarium avenaceum	EC90	=	38.0	ug ml-1	PMID[544199]
NPT1198	Organism	Magnaporthe grisea	Magnaporthe grisea	MIC	=	3.0	ug.mL-1	PMID[544199]
NPT1198	Organism	Magnaporthe grisea	Magnaporthe grisea	EC90	=	8.0	ug ml-1	PMID[544199]
NPT3821	Organism	Alternaria citri	Alternaria citri	EC50	=	44.0	ug.mL-1	PMID[544199]

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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 NPC73422 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	342
0.1-0.2	1307
0.2-0.3	2983
0.3-0.4	6578
0.4-0.5	11104
0.5-0.6	6131
0.6-0.7	6358
0.7-0.8	7722
0.8-0.85	152
0.85-0.9	5
0.9-0.95	10
0.95-1	5

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Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC310399
0.9934	High Similarity	NPC209473
0.9934	High Similarity	NPC329743
0.9804	High Similarity	NPC90336
0.9437	High Similarity	NPC254071

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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 NPC73422 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	287
0.1-0.2	815
0.2-0.3	1721
0.3-0.4	2570
0.4-0.5	2064
0.5-0.6	1127
0.6-0.7	428
0.7-0.8	134
0.8-0.85	4
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
0.8589	High Similarity	NPD7199	Phase 2
0.8373	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.8077	Intermediate Similarity	NPD6004	Phase 3
0.8077	Intermediate Similarity	NPD6006	Clinical (unspecified phase)
0.8077	Intermediate Similarity	NPD6003	Clinical (unspecified phase)

Showing 1 to 5 of 200 entries

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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