NPASS Compound

Structure

CID135685 OpenBabel06191715492D 35 39 0 0 1 0 0 0 0 0999 V2000 3.9518 -1.5636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8444 4.3875 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2624 -0.8742 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8444 3.4125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3983 0.5723 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6887 3.9000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1460 -0.3695 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8444 4.3875 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7089 1.2617 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6887 2.9250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8444 -0.4875 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6887 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1359 1.4465 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5730 -0.1847 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8444 2.4375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1273 -0.9667 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1762 1.8194 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2042 -0.6218 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 3.9000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8836 0.5047 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7671 1.0094 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8444 2.4375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8444 1.4625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0777 1.6988 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 0.9750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8444 1.4625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5148 0.0676 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 2.9250 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6887 0.9750 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0280 -1.3398 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1512 1.8194 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3300 2.6406 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6887 0.9750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6637 0.9750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 18 1 0 0 0 0 2 19 1 0 0 0 0 5 7 1 0 0 0 0 5 9 1 0 0 0 0 6 8 1 0 0 0 0 6 10 1 0 0 0 0 7 18 1 0 0 0 0 8 19 1 0 0 0 0 9 21 2 0 0 0 0 10 22 2 0 0 0 0 11 12 1 0 0 0 0 11 29 1 0 0 0 0 12 30 1 0 0 0 0 13 20 2 0 0 0 0 13 24 1 0 0 0 0 14 20 1 0 0 0 0 14 27 1 0 0 0 0 15 23 1 0 0 0 0 15 28 1 0 0 0 0 16 31 1 0 0 0 0 17 30 1 0 0 0 0 17 32 1 0 0 0 0 18 27 1 6 0 0 0 19 28 1 1 0 0 0 20 29 1 0 0 0 0 21 24 1 0 0 0 0 21 27 1 0 0 0 0 22 26 1 0 0 0 0 22 28 1 0 0 0 0 23 25 2 0 0 0 0 23 30 1 0 0 0 0 24 33 2 0 0 0 0 25 26 1 0 0 0 0 25 29 1 0 0 0 0 26 34 2 0 0 0 0 27 3 1 6 0 0 0 28 4 1 1 0 0 0 29 16 1 1 0 0 0 30 35 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	480.29
Volume:	512.786
LogP:	3.519
LogD:	1.813
LogS:	-3.856
# Rotatable Bonds:	3
TPSA:	94.83
# H-Bond Aceptor:	5
# H-Bond Donor:	3
# Rings:	5
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.529
Synthetic Accessibility Score:	5.76
Fsp3:	0.667
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:	-4.775
MDCK Permeability:	2.3682565370108932e-05
Pgp-inhibitor:	0.896
Pgp-substrate:	0.569
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.002

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.912
Plasma Protein Binding (PPB):	92.58645629882812%
Volume Distribution (VD):	1.329
Pgp-substrate:	8.432669639587402%

ADMET: Metabolism

CYP1A2-inhibitor:	0.023
CYP1A2-substrate:	0.622
CYP2C19-inhibitor:	0.031
CYP2C19-substrate:	0.734
CYP2C9-inhibitor:	0.033
CYP2C9-substrate:	0.032
CYP2D6-inhibitor:	0.008
CYP2D6-substrate:	0.038
CYP3A4-inhibitor:	0.945
CYP3A4-substrate:	0.472

ADMET: Excretion

Clearance (CL):	8.653
Half-life (T1/2):	0.048

ADMET: Toxicity

hERG Blockers:	0.004
Human Hepatotoxicity (H-HT):	0.172
Drug-inuced Liver Injury (DILI):	0.029
AMES Toxicity:	0.02
Rat Oral Acute Toxicity:	0.902
Maximum Recommended Daily Dose:	0.914
Skin Sensitization:	0.062
Carcinogencity:	0.828
Eye Corrosion:	0.023
Eye Irritation:	0.014
Respiratory Toxicity:	0.992

Download Data

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

Natural Product: NPC135685

Natural Product ID:	NPC135685
*Common Name:**	Diincarvilone A
IUPAC Name:	(4S,4aR,5S,8R)-8-[(8S,8aR)-8,8a-dimethyl-4-oxo-1,6,7,8-tetrahydronaphthalen-2-yl]-5-hydroxy-5,8-bis(hydroxymethyl)-4,4a-dimethyl-2,3,4,6,7,10-hexahydroanthracen-9-one
Synonyms:	Diincarvilone A
Standard InCHIKey:	ZXTFCVATBJFEBU-XXAMNUPESA-N
Standard InCHI:	InChI=1S/C30H40O5/c1-18-7-5-9-21-24(33)13-20(14-27(18,21)3)29(16-31)11-12-30(35,17-32)23-15-28(4)19(2)8-6-10-22(28)26(34)25(23)29/h9-10,13,18-19,31-32,35H,5-8,11-12,14-17H2,1-4H3/t18-,19-,27+,28+,29+,30+/m0/s1
SMILES:	C[C@H]1CCC=C2C(=O)C=C(C[C@]12C)[C@@]1(CC[C@@](CO)(C2=C1C(=O)C1=CCC[C@H](C)[C@@]1(C)C2)O)CO
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2062966
PubChem CID:	60155322
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0003655] Eremophilane, 8,9-secoeremophilane and furoeremophilane sesquiterpenoids

*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
NPO21937	Incarvillea arguta	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22620677]
NPO21937	Incarvillea arguta	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18120	Radix rehmanniae	Species	Lymnaeidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21937	Incarvillea arguta	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21937	Incarvillea arguta	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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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

Activity Type	# Activity
Cell Line	4

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Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell Line	HL-60	Homo sapiens	IC50	>	40000.0	nM	PMID[447463]
NPT659	Cell Line	SMMC-7721	Homo sapiens	IC50	>	40000.0	nM	PMID[447463]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	>	40000.0	nM	PMID[447463]
NPT660	Cell Line	SW480	Homo sapiens	IC50	>	40000.0	nM	PMID[447463]

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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 NPC135685 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	214
0.1-0.2	1260
0.2-0.3	4872
0.3-0.4	11450
0.4-0.5	13225
0.5-0.6	7710
0.6-0.7	3675
0.7-0.8	279
0.8-0.85	8
0.85-0.9	1
0.9-0.95	1
0.95-1	2

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Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC470522
0.9	High Similarity	NPC470523
0.8901	High Similarity	NPC470524
0.8421	Intermediate Similarity	NPC116726
0.828	Intermediate Similarity	NPC472974

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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 NPC135685 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	198
0.1-0.2	1833
0.2-0.3	3868
0.3-0.4	2282
0.4-0.5	582
0.5-0.6	295
0.6-0.7	92
0.7-0.8	0
0.8-0.85	0
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
0.75	Intermediate Similarity	NPD7515	Phase 2
0.7347	Intermediate Similarity	NPD3618	Phase 1
0.7281	Intermediate Similarity	NPD7115	Discovery
0.7263	Intermediate Similarity	NPD4695	Discontinued
0.7184	Intermediate Similarity	NPD7748	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