NPASS Compound

Structure

CID185590 OpenBabel06191715562D 27 30 0 0 1 0 0 0 0 0999 V2000 -0.8645 -0.5027 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1366 1.0375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 4.9039 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0776 2.8695 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4461 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7341 -0.4178 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4307 2.7499 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1691 2.0874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.6704 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4461 3.3398 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8772 1.9650 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7120 2.0882 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5463 2.5678 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 3.3398 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2687 1.2978 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7230 2.0874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4461 0.8351 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 0.8351 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4461 1.6704 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7054 3.0882 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 1.8976 4.1218 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8791 3.1764 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4507 0.4133 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7747 1.8648 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4515 4.1218 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6261 2.0874 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 21 1 0 0 0 0 2 25 1 0 0 0 0 3 26 1 0 0 0 0 4 27 1 0 0 0 0 5 6 1 0 0 0 0 5 17 1 0 0 0 0 6 21 1 0 0 0 0 7 11 2 0 0 0 0 7 13 1 0 0 0 0 8 10 1 0 0 0 0 8 17 1 0 0 0 0 9 12 1 0 0 0 0 10 14 1 0 0 0 0 10 22 2 0 0 0 0 11 15 1 0 0 0 0 11 25 1 0 0 0 0 12 19 1 6 0 0 0 12 20 1 0 0 0 0 13 19 1 0 0 0 0 13 23 2 0 0 0 0 14 16 2 0 0 0 0 14 26 1 0 0 0 0 15 19 1 6 0 0 0 15 24 1 0 0 0 0 16 18 1 0 0 0 0 16 27 1 0 0 0 0 17 18 1 6 0 0 0 18 9 1 1 0 0 0 18 21 1 0 0 0 0 19 17 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	397.13
Volume:	371.358
LogP:	1.053
LogD:	0.589
LogS:	-2.634
# Rotatable Bonds:	3
TPSA:	82.14
# H-Bond Aceptor:	7
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.52
Synthetic Accessibility Score:	5.728
Fsp3:	0.737
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.926
MDCK Permeability:	5.026617509429343e-05
Pgp-inhibitor:	0.006
Pgp-substrate:	0.989
Human Intestinal Absorption (HIA):	0.014
20% Bioavailability (F20%):	0.369
30% Bioavailability (F30%):	0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.93
Plasma Protein Binding (PPB):	30.817832946777344%
Volume Distribution (VD):	1.098
Pgp-substrate:	68.54439544677734%

ADMET: Metabolism

CYP1A2-inhibitor:	0.008
CYP1A2-substrate:	0.982
CYP2C19-inhibitor:	0.018
CYP2C19-substrate:	0.903
CYP2C9-inhibitor:	0.003
CYP2C9-substrate:	0.046
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.161
CYP3A4-inhibitor:	0.241
CYP3A4-substrate:	0.948

ADMET: Excretion

Clearance (CL):	8.017
Half-life (T1/2):	0.245

ADMET: Toxicity

hERG Blockers:	0.005
Human Hepatotoxicity (H-HT):	0.677
Drug-inuced Liver Injury (DILI):	0.201
AMES Toxicity:	0.331
Rat Oral Acute Toxicity:	0.931
Maximum Recommended Daily Dose:	0.498
Skin Sensitization:	0.056
Carcinogencity:	0.974
Eye Corrosion:	0.088
Eye Irritation:	0.022
Respiratory Toxicity:	0.987

Download Data

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

Natural Product: NPC185590

Natural Product ID:	NPC185590
*Common Name:**	Dauricumine
IUPAC Name:	n.a.
Synonyms:	Dauricumine
Standard InCHIKey:	FSXRARBVZZKCGJ-WPLONRSQSA-N
Standard InCHI:	InChI=1S/C19H24ClNO6/c1-21-6-5-17-8-10(22)14(26-3)16(27-4)18(17,21)9-12(20)19(17)13(23)7-11(25-2)15(19)24/h7,12,15,24H,5-6,8-9H2,1-4H3/t12-,15-,17+,18+,19+/m0/s1
SMILES:	CN1CC[C@@]23CC(=O)C(=C([C@@]12C[C@@H]([C@@]13C(=O)C=C([C@@H]1O)OC)Cl)OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL391835
PubChem CID:	11741544
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
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.3987/COM-96-7609.]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16038566]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	stem	n.a.	PMID[16964757]
NPO20751	Hypserpa nitida	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17723297]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18081254]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23059629]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
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	=	2193000.0	nM	PMID[464296]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	=	1312000.0	nM	PMID[464296]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	>	3291000.0	nM	PMID[464296]
NPT2	Others	Unspecified		Ratio CC50/IC50	=	1.67	n.a.	PMID[464296]
NPT2	Others	Unspecified		Ratio CC50/IC50	<	1.0	n.a.	PMID[464296]

☑ 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 NPC185590 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	175
0.1-0.2	1257
0.2-0.3	7511
0.3-0.4	22842
0.4-0.5	9809
0.5-0.6	1070
0.6-0.7	26
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	2
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC15440
1.0	High Similarity	NPC264958
0.9571	High Similarity	NPC44200
0.9571	High Similarity	NPC12124
0.9286	High Similarity	NPC266697
0.9259	High Similarity	NPC45813
0.6755	Remote Similarity	NPC470539
0.6733	Remote Similarity	NPC476951
0.6443	Remote Similarity	NPC88190
0.6419	Remote Similarity	NPC476952
0.6387	Remote Similarity	NPC215507
0.6093	Remote Similarity	NPC235625
0.6078	Remote Similarity	NPC23963
0.6054	Remote Similarity	NPC473232
0.6026	Remote Similarity	NPC474371
0.5987	Remote Similarity	NPC106791
0.5987	Remote Similarity	NPC201889
0.5987	Remote Similarity	NPC96731
0.5918	Remote Similarity	NPC470535
0.5909	Remote Similarity	NPC11379
0.5909	Remote Similarity	NPC230849
0.5882	Remote Similarity	NPC471673
0.5879	Remote Similarity	NPC88943
0.5878	Remote Similarity	NPC470536
0.5871	Remote Similarity	NPC238323
0.586	Remote Similarity	NPC204639
0.5849	Remote Similarity	NPC471086
0.5838	Remote Similarity	NPC314050
0.5838	Remote Similarity	NPC315809
0.5828	Remote Similarity	NPC193471
0.5828	Remote Similarity	NPC130124
0.5817	Remote Similarity	NPC147707
0.58	Remote Similarity	NPC470534
0.58	Remote Similarity	NPC47857
0.58	Remote Similarity	NPC181510
0.58	Remote Similarity	NPC168758
0.5799	Remote Similarity	NPC276822
0.5796	Remote Similarity	NPC280498
0.5793	Remote Similarity	NPC70369
0.5786	Remote Similarity	NPC470537
0.5779	Remote Similarity	NPC156336
0.5779	Remote Similarity	NPC200412
0.5779	Remote Similarity	NPC120599
0.5776	Remote Similarity	NPC477988
0.5774	Remote Similarity	NPC803
0.5772	Remote Similarity	NPC474725
0.5767	Remote Similarity	NPC313348
0.5767	Remote Similarity	NPC475987
0.5762	Remote Similarity	NPC474497
0.5758	Remote Similarity	NPC230889
0.575	Remote Similarity	NPC173173
0.574	Remote Similarity	NPC956
0.5695	Remote Similarity	NPC30911
0.5695	Remote Similarity	NPC316984
0.5689	Remote Similarity	NPC25025
0.5687	Remote Similarity	NPC280903
0.5677	Remote Similarity	NPC284656
0.5677	Remote Similarity	NPC471109
0.5669	Remote Similarity	NPC472001
0.5667	Remote Similarity	NPC471400
0.5664	Remote Similarity	NPC135576
0.5664	Remote Similarity	NPC93271
0.566	Remote Similarity	NPC477985
0.566	Remote Similarity	NPC326386
0.566	Remote Similarity	NPC471087
0.5658	Remote Similarity	NPC275100
0.5658	Remote Similarity	NPC35069
0.5658	Remote Similarity	NPC314550
0.5658	Remote Similarity	NPC258711
0.5655	Remote Similarity	NPC473396
0.5649	Remote Similarity	NPC202722
0.5649	Remote Similarity	NPC39041
0.5649	Remote Similarity	NPC471846
0.5649	Remote Similarity	NPC241294
0.5649	Remote Similarity	NPC471845
0.5644	Remote Similarity	NPC120335
0.5641	Remote Similarity	NPC323532
0.5641	Remote Similarity	NPC35037
0.564	Remote Similarity	NPC201899
0.564	Remote Similarity	NPC471674
0.5638	Remote Similarity	NPC475800
0.5634	Remote Similarity	NPC469819
0.5634	Remote Similarity	NPC114162
0.5629	Remote Similarity	NPC470529
0.5629	Remote Similarity	NPC470531
0.5629	Remote Similarity	NPC470533
0.5629	Remote Similarity	NPC470527
0.5629	Remote Similarity	NPC470530
0.5629	Remote Similarity	NPC196073
0.5629	Remote Similarity	NPC195435
0.5629	Remote Similarity	NPC470532
0.5629	Remote Similarity	NPC470528
0.5617	Remote Similarity	NPC471471
0.5617	Remote Similarity	NPC164476
0.5616	Remote Similarity	NPC471401
0.5602	Remote Similarity	NPC243902

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 NPC185590 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	119
0.1-0.2	968
0.2-0.3	3981
0.3-0.4	3358
0.4-0.5	670
0.5-0.6	53
0.6-0.7	1
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
0.5901	Remote Similarity	NPD6845	Suspended
0.5818	Remote Similarity	NPD6333	Approved
0.5818	Remote Similarity	NPD6334	Approved
0.575	Remote Similarity	NPD6033	Approved
0.5741	Remote Similarity	NPD7260	Phase 2
0.574	Remote Similarity	NPD5193	Discontinued
0.5714	Remote Similarity	NPD8384	Approved
0.5695	Remote Similarity	NPD2204	Approved
0.5652	Remote Similarity	NPD8337	Approved
0.5652	Remote Similarity	NPD8336	Approved

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