NPASS Compound

Structure

NPC474059 OpenBabel07101719152D 28 31 0 0 1 0 0 0 0 0999 V2000 5.2812 -1.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2257 4.2541 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0850 -3.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4152 -1.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9890 1.8271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5823 0.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4013 2.6361 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 1.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 -0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 -1.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 -3.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 -1.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 0.3090 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 0.9511 1.3090 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.6831 -1.6910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8171 -0.1910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6831 -2.6910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5878 0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4067 2.5316 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9511 0.3090 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.8171 -3.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 -4.1910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 -4.1910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1810 3.3406 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9511 -2.6910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 4 1 0 0 0 0 2 27 1 0 0 0 0 3 28 1 0 0 0 0 4 13 2 0 0 0 0 5 6 2 0 0 0 0 5 7 1 0 0 0 0 6 19 1 0 0 0 0 7 20 2 0 0 0 0 8 9 1 0 0 0 0 8 14 1 0 0 0 0 9 15 1 0 0 0 0 10 13 1 0 0 0 0 10 14 1 0 0 0 0 11 16 1 0 0 0 0 12 25 1 0 0 0 0 13 16 1 0 0 0 0 14 17 1 0 0 0 0 15 21 1 0 0 0 0 15 22 1 0 0 0 0 16 18 1 1 0 0 0 17 11 1 1 0 0 0 17 22 1 0 0 0 0 18 12 1 6 0 0 0 18 23 1 0 0 0 0 19 21 2 0 0 0 0 19 24 1 0 0 0 0 20 21 1 0 0 0 0 20 27 1 0 0 0 0 22 24 1 0 0 0 0 23 26 2 0 0 0 0 23 28 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	385.23
Volume:	405.114
LogP:	3.825
LogD:	3.679
LogS:	-4.826
# Rotatable Bonds:	5
TPSA:	67.79
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.61
Synthetic Accessibility Score:	4.715
Fsp3:	0.609
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.699
MDCK Permeability:	1.4889371414028574e-05
Pgp-inhibitor:	0.455
Pgp-substrate:	0.007
Human Intestinal Absorption (HIA):	0.27
20% Bioavailability (F20%):	0.008
30% Bioavailability (F30%):	0.359

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.658
Plasma Protein Binding (PPB):	90.31336212158203%
Volume Distribution (VD):	0.96
Pgp-substrate:	4.6956939697265625%

ADMET: Metabolism

CYP1A2-inhibitor:	0.231
CYP1A2-substrate:	0.848
CYP2C19-inhibitor:	0.886
CYP2C19-substrate:	0.914
CYP2C9-inhibitor:	0.78
CYP2C9-substrate:	0.489
CYP2D6-inhibitor:	0.097
CYP2D6-substrate:	0.881
CYP3A4-inhibitor:	0.95
CYP3A4-substrate:	0.813

ADMET: Excretion

Clearance (CL):	6.726
Half-life (T1/2):	0.248

ADMET: Toxicity

hERG Blockers:	0.035
Human Hepatotoxicity (H-HT):	0.358
Drug-inuced Liver Injury (DILI):	0.521
AMES Toxicity:	0.024
Rat Oral Acute Toxicity:	0.333
Maximum Recommended Daily Dose:	0.802
Skin Sensitization:	0.049
Carcinogencity:	0.051
Eye Corrosion:	0.003
Eye Irritation:	0.011
Respiratory Toxicity:	0.813

Download Data

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

Natural Product: NPC474059

Natural Product ID:	NPC474059
*Common Name:**	9-Methoxy 16(R),E-Isositsirikine
IUPAC Name:	methyl (2R)-2-[(2R,3E,11bR)-3-ethylidene-7-methoxy-1,2,4,4a,5,6,6a,11,11a,11b-decahydrobenzo[a]carbazol-2-yl]-3-hydroxypropanoate
Synonyms:	9-Methoxy 16(R),E-Isositsirikine
Standard InCHIKey:	PGOBOWWFWXOGHZ-FCJHPKDCSA-N
Standard InCHI:	InChI=1S/C23H31NO4/c1-4-13-10-14-8-9-15-21-19(6-5-7-20(21)27-2)24-22(15)17(14)11-16(13)18(12-25)23(26)28-3/h4-7,14-18,22,24-25H,8-12H2,1-3H3/b13-4+/t14?,15?,16-,17+,18-,22?/m0/s1
SMILES:	COC(=O)[C@H]([C@H]1C[C@@H]2C(C/C/1=CC)CCC1C2Nc2c1c(OC)ccc2)CO
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL459422
PubChem CID:	44559928
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0000210] Carbazoles

*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
NPO33506	strychnos lucens	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12398531]

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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	3
Others	3

Activity Type	# Activity
Organism	6

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Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	13600.0	nM	PMID[569814]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	9900.0	nM	PMID[569814]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	12500.0	nM	PMID[569814]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC90	=	34600.0	nM	PMID[569814]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC90	=	36300.0	nM	PMID[569814]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC90	=	37800.0	nM	PMID[569814]

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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 NPC474059 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	245
0.1-0.2	1139
0.2-0.3	3946
0.3-0.4	12086
0.4-0.5	8926
0.5-0.6	14136
0.6-0.7	2068
0.7-0.8	149
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

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Similarity Score	Similarity Level	Natural Product ID
0.8085	Intermediate Similarity	NPC230313
0.799	Intermediate Similarity	NPC87714
0.7989	Intermediate Similarity	NPC243626
0.7927	Intermediate Similarity	NPC232600
0.7926	Intermediate Similarity	NPC22476

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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 NPC474059 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	164
0.1-0.2	517
0.2-0.3	764
0.3-0.4	1408
0.4-0.5	2472
0.5-0.6	2884
0.6-0.7	914
0.7-0.8	27
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
0.7869	Intermediate Similarity	NPD7479	Phase 2
0.7772	Intermediate Similarity	NPD4668	Phase 2
0.7657	Intermediate Similarity	NPD814	Clinical (unspecified phase)
0.7653	Intermediate Similarity	NPD6238	Discontinued
0.7629	Intermediate Similarity	NPD7238	Clinical (unspecified phase)

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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