NPASS Compound

Structure

NPC266697 OpenBabel07101718222D 30 33 0 0 1 0 0 0 0 0999 V2000 3.0433 -1.8178 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5419 0.4320 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9494 0.2018 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7213 3.5612 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1193 3.0759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9927 -1.6160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2420 -0.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3600 -0.7852 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3948 -0.8867 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8450 0.9778 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4024 0.6495 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9231 1.5988 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6432 0.0284 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4024 1.6200 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8884 1.7003 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0044 1.4631 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5618 2.1053 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6779 -0.0731 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7213 1.6200 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5618 0.1642 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7213 0.6495 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2831 0.8136 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3736 2.5408 0.0000 Cl 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 4.2926 -0.6929 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.0835 2.5906 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9030 2.4283 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1926 -0.9136 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5618 3.0759 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1193 2.1053 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 2 7 1 0 0 0 0 3 24 1 0 0 0 0 4 29 1 0 0 0 0 5 30 1 0 0 0 0 6 25 1 0 0 0 0 7 25 1 0 0 0 0 8 9 1 0 0 0 0 8 20 1 0 0 0 0 9 24 1 0 0 0 0 10 13 2 0 0 0 0 10 16 1 0 0 0 0 11 14 1 0 0 0 0 11 20 1 0 0 0 0 12 15 1 0 0 0 0 13 18 1 0 0 0 0 13 25 1 0 0 0 0 14 17 1 0 0 0 0 14 26 2 0 0 0 0 15 22 1 6 0 0 0 15 23 1 0 0 0 0 16 22 1 0 0 0 0 16 27 2 0 0 0 0 17 19 2 0 0 0 0 17 29 1 0 0 0 0 18 22 1 6 0 0 0 18 28 1 0 0 0 0 19 21 1 0 0 0 0 19 30 1 0 0 0 0 20 21 1 6 0 0 0 21 12 1 1 0 0 0 21 24 1 0 0 0 0 22 20 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	438.19
Volume:	425.452
LogP:	1.855
LogD:	0.937
LogS:	-2.557
# Rotatable Bonds:	5
TPSA:	76.15
# H-Bond Aceptor:	7
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.478
Synthetic Accessibility Score:	5.702
Fsp3:	0.773
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.835
MDCK Permeability:	2.4464183297823183e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.992
Human Intestinal Absorption (HIA):	0.015
20% Bioavailability (F20%):	0.437
30% Bioavailability (F30%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.973
Plasma Protein Binding (PPB):	25.649517059326172%
Volume Distribution (VD):	1.59
Pgp-substrate:	77.62232971191406%

ADMET: Metabolism

CYP1A2-inhibitor:	0.007
CYP1A2-substrate:	0.957
CYP2C19-inhibitor:	0.023
CYP2C19-substrate:	0.906
CYP2C9-inhibitor:	0.004
CYP2C9-substrate:	0.074
CYP2D6-inhibitor:	0.012
CYP2D6-substrate:	0.306
CYP3A4-inhibitor:	0.132
CYP3A4-substrate:	0.944

ADMET: Excretion

Clearance (CL):	11.337
Half-life (T1/2):	0.294

ADMET: Toxicity

hERG Blockers:	0.005
Human Hepatotoxicity (H-HT):	0.716
Drug-inuced Liver Injury (DILI):	0.077
AMES Toxicity:	0.068
Rat Oral Acute Toxicity:	0.891
Maximum Recommended Daily Dose:	0.928
Skin Sensitization:	0.054
Carcinogencity:	0.96
Eye Corrosion:	0.007
Eye Irritation:	0.01
Respiratory Toxicity:	0.989

Download Data

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

Natural Product: NPC266697

Natural Product ID:	NPC266697
*Common Name:**	Hypserpanine A
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	GSPWOIUNBWNJMP-NIXKLGBSSA-N
Standard InCHI:	InChI=1S/C22H31ClN2O5/c1-6-25(7-2)13-10-16(27)22(18(13)28)15(23)12-21-19(30-5)17(29-4)14(26)11-20(21,22)8-9-24(21)3/h10,15,18,28H,6-9,11-12H2,1-5H3/t15-,18-,20+,21+,22+/m0/s1
SMILES:	CCN(CC)C1=CC(=O)[C@]2([C@H](C[C@@]34C(=C(C(=O)C[C@@]23CCN4C)OC)OC)Cl)[C@H]1O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL234980
PubChem CID:	44433882
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002791] Acutumine and related alkaloids

*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

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO20751	Hypserpa nitida	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17723297]
NPO20751	Hypserpa nitida	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ 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

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ 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	2
Others	3

Activity Type	# Activity
NON-MOLECULAR	1
Organism	2
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	CC50	=	2226000.0	nM	PMID[550000]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	=	1415000.0	nM	PMID[550000]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	>	2870000.0	nM	PMID[550000]
NPT2	Others	Unspecified		Ratio CC50/IC50	=	1.57	n.a.	PMID[550000]
NPT2	Others	Unspecified		Ratio CC50/IC50	<	1.0	n.a.	PMID[550000]

☑ 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 NPC266697 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	171
0.1-0.2	1211
0.2-0.3	8640
0.3-0.4	23624
0.4-0.5	8527
0.5-0.6	503
0.6-0.7	14
0.7-0.8	0
0.8-0.85	0
0.85-0.9	3
0.9-0.95	3
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9286	High Similarity	NPC264958
0.9286	High Similarity	NPC15440
0.9286	High Similarity	NPC185590
0.8897	High Similarity	NPC12124
0.8897	High Similarity	NPC44200
0.8571	High Similarity	NPC45813
0.6513	Remote Similarity	NPC476951
0.6429	Remote Similarity	NPC470539
0.6419	Remote Similarity	NPC476952
0.6333	Remote Similarity	NPC88190
0.6276	Remote Similarity	NPC473232
0.6076	Remote Similarity	NPC215507
0.5918	Remote Similarity	NPC470535
0.5882	Remote Similarity	NPC96731
0.5878	Remote Similarity	NPC470536
0.5839	Remote Similarity	NPC315011
0.5802	Remote Similarity	NPC133089
0.58	Remote Similarity	NPC470534
0.5786	Remote Similarity	NPC470537
0.5779	Remote Similarity	NPC235625
0.5779	Remote Similarity	NPC471673
0.5769	Remote Similarity	NPC23963
0.5769	Remote Similarity	NPC238323
0.5767	Remote Similarity	NPC475987
0.5767	Remote Similarity	NPC313348
0.5747	Remote Similarity	NPC314050
0.5747	Remote Similarity	NPC315809
0.5741	Remote Similarity	NPC120335
0.5714	Remote Similarity	NPC147707
0.5689	Remote Similarity	NPC25025
0.5687	Remote Similarity	NPC280903
0.5679	Remote Similarity	NPC307165
0.5677	Remote Similarity	NPC106791
0.5677	Remote Similarity	NPC201889
0.5652	Remote Similarity	NPC471086
0.5649	Remote Similarity	NPC288629
0.5629	Remote Similarity	NPC470530
0.5629	Remote Similarity	NPC470531
0.5629	Remote Similarity	NPC470529
0.5629	Remote Similarity	NPC470533
0.5629	Remote Similarity	NPC470528
0.5629	Remote Similarity	NPC470527
0.5629	Remote Similarity	NPC470532
0.5625	Remote Similarity	NPC474371
0.5614	Remote Similarity	NPC276822
0.5605	Remote Similarity	NPC11379
0.5605	Remote Similarity	NPC230849

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 NPC266697 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	118
0.1-0.2	760
0.2-0.3	3807
0.3-0.4	3785
0.4-0.5	653
0.5-0.6	27
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5839	Remote Similarity	NPD2101	Approved
0.5818	Remote Similarity	NPD6334	Approved
0.5818	Remote Similarity	NPD6333	Approved
0.5802	Remote Similarity	NPD6845	Suspended
0.5644	Remote Similarity	NPD7260	Phase 2

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