NPASS Compound

Structure

NPC57163 OpenBabel07101718192D 34 38 0 0 1 0 0 0 0 0999 V2000 8.6603 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 2.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -2.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 2.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4641 1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 6.0622 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3301 1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 -0.0000 0.0000 N 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 -0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3 22 1 0 0 0 0 4 32 1 0 0 0 0 5 8 1 0 0 0 0 5 9 1 0 0 0 0 6 10 1 0 0 0 0 6 12 1 0 0 0 0 7 11 1 0 0 0 0 7 13 1 0 0 0 0 8 25 1 0 0 0 0 9 26 1 0 0 0 0 10 27 1 0 0 0 0 11 28 1 0 0 0 0 12 32 1 0 0 0 0 13 33 1 0 0 0 0 14 20 1 0 0 0 0 14 23 1 0 0 0 0 15 21 1 0 0 0 0 15 24 1 0 0 0 0 16 20 1 0 0 0 0 17 21 1 0 0 0 0 18 23 1 0 0 0 0 19 24 1 0 0 0 0 20 1 1 6 0 0 0 21 2 1 6 0 0 0 22 33 1 0 0 0 0 22 34 2 0 0 0 0 23 27 2 0 0 0 0 24 28 2 0 0 0 0 25 18 1 6 0 0 0 25 31 1 0 0 0 0 26 19 1 1 0 0 0 26 31 1 0 0 0 0 27 29 1 0 0 0 0 28 30 1 0 0 0 0 29 16 1 6 0 0 0 29 32 1 0 0 0 0 30 17 1 6 0 0 0 30 33 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	467.39
Volume:	518.525
LogP:	3.917
LogD:	4.273
LogS:	-2.658
# Rotatable Bonds:	5
TPSA:	35.58
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	5
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.528
Synthetic Accessibility Score:	4.937
Fsp3:	0.833
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-5.393
MDCK Permeability:	5.811585197079694e-06
Pgp-inhibitor:	0.028
Pgp-substrate:	0.946
Human Intestinal Absorption (HIA):	0.035
20% Bioavailability (F20%):	0.468
30% Bioavailability (F30%):	0.015

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.15
Plasma Protein Binding (PPB):	57.668373107910156%
Volume Distribution (VD):	0.593
Pgp-substrate:	36.913883209228516%

ADMET: Metabolism

CYP1A2-inhibitor:	0.028
CYP1A2-substrate:	0.088
CYP2C19-inhibitor:	0.377
CYP2C19-substrate:	0.774
CYP2C9-inhibitor:	0.157
CYP2C9-substrate:	0.064
CYP2D6-inhibitor:	0.933
CYP2D6-substrate:	0.77
CYP3A4-inhibitor:	0.79
CYP3A4-substrate:	0.631

ADMET: Excretion

Clearance (CL):	5.015
Half-life (T1/2):	0.067

ADMET: Toxicity

hERG Blockers:	0.859
Human Hepatotoxicity (H-HT):	0.994
Drug-inuced Liver Injury (DILI):	0.776
AMES Toxicity:	0.014
Rat Oral Acute Toxicity:	0.13
Maximum Recommended Daily Dose:	0.993
Skin Sensitization:	0.918
Carcinogencity:	0.92
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.973

Download Data

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

Natural Product: NPC57163

Natural Product ID:	NPC57163
*Common Name:**	Cryptadine A
IUPAC Name:	1-[(7S,8aS)-5-[[(2R,6R)-6-[[(7S,8aS)-1,7-dimethyl-3,4,6,7,8,8a-hexahydro-2H-quinolin-5-yl]methyl]piperidin-2-yl]methyl]-7-methyl-3,4,6,7,8,8a-hexahydro-2H-quinolin-1-yl]ethanone
Synonyms:
Standard InCHIKey:	GNBIIUGCLQZEQB-JIWCGRIKSA-N
Standard InCHI:	InChI=1S/C30H49N3O/c1-20-14-23(27-10-6-12-32(4)29(27)16-20)18-25-8-5-9-26(31-25)19-24-15-21(2)17-30-28(24)11-7-13-33(30)22(3)34/h20-21,25-26,29-31H,5-19H2,1-4H3/t20-,21-,25+,26+,29-,30-/m0/s1
SMILES:	C[C@H]1CC(=C2CCCN(C)[C@H]2C1)C[C@H]1CCC[C@H](CC2=C3CCCN(C(=O)C)[C@H]3C[C@@H](C)C2)N1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL238809
PubChem CID:	44437888
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000195] Piperidines [CHEMONTID:0000335] N-acylpiperidines

*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
NPO33447	lycopodium cryptomerinum	Species	Lycopodiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17904850]

☑ 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	1

Activity Type	# Activity
Individual Protein	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT914	Individual Protein	Acetylcholinesterase	Bos taurus	IC50	=	106300.0	nM	PMID[456491]

☑ 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 NPC57163 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	100
0.1-0.2	5756
0.2-0.3	23011
0.3-0.4	12038
0.4-0.5	1533
0.5-0.6	204
0.6-0.7	45
0.7-0.8	8
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC116881
0.7356	Intermediate Similarity	NPC268580
0.7326	Intermediate Similarity	NPC308050
0.7241	Intermediate Similarity	NPC39308
0.7159	Intermediate Similarity	NPC120699
0.7159	Intermediate Similarity	NPC127430
0.6774	Remote Similarity	NPC61321
0.6774	Remote Similarity	NPC78058
0.6774	Remote Similarity	NPC234822
0.6774	Remote Similarity	NPC207048
0.6774	Remote Similarity	NPC143344
0.6774	Remote Similarity	NPC135639
0.6739	Remote Similarity	NPC215474
0.6737	Remote Similarity	NPC43308
0.6667	Remote Similarity	NPC477460
0.6667	Remote Similarity	NPC76869
0.6522	Remote Similarity	NPC12035
0.6458	Remote Similarity	NPC157479
0.6354	Remote Similarity	NPC147513
0.63	Remote Similarity	NPC145707
0.6277	Remote Similarity	NPC474122
0.6264	Remote Similarity	NPC25110
0.6237	Remote Similarity	NPC267203
0.6237	Remote Similarity	NPC77890
0.6237	Remote Similarity	NPC132858
0.6136	Remote Similarity	NPC48448
0.6136	Remote Similarity	NPC266383
0.6136	Remote Similarity	NPC180401
0.6136	Remote Similarity	NPC206241
0.6136	Remote Similarity	NPC271803
0.6136	Remote Similarity	NPC290231
0.6136	Remote Similarity	NPC68043
0.6117	Remote Similarity	NPC25033
0.6117	Remote Similarity	NPC119225
0.6117	Remote Similarity	NPC470382
0.6117	Remote Similarity	NPC476261
0.6117	Remote Similarity	NPC471635
0.6105	Remote Similarity	NPC152039
0.6105	Remote Similarity	NPC118329
0.6075	Remote Similarity	NPC58200
0.6071	Remote Similarity	NPC477459
0.6071	Remote Similarity	NPC143173
0.6071	Remote Similarity	NPC477461
0.6064	Remote Similarity	NPC211322
0.6044	Remote Similarity	NPC17770
0.6042	Remote Similarity	NPC472312
0.6	Remote Similarity	NPC91036
0.5938	Remote Similarity	NPC329782
0.5938	Remote Similarity	NPC90150
0.5914	Remote Similarity	NPC214125
0.5914	Remote Similarity	NPC320667
0.5904	Remote Similarity	NPC231129
0.5849	Remote Similarity	NPC474164
0.5833	Remote Similarity	NPC100810
0.5833	Remote Similarity	NPC82919
0.5833	Remote Similarity	NPC144714
0.5824	Remote Similarity	NPC265789
0.5816	Remote Similarity	NPC171639
0.5814	Remote Similarity	NPC472544
0.5806	Remote Similarity	NPC63284
0.5806	Remote Similarity	NPC80447
0.5769	Remote Similarity	NPC476753
0.5769	Remote Similarity	NPC476752
0.5747	Remote Similarity	NPC206660
0.5728	Remote Similarity	NPC84171
0.5714	Remote Similarity	NPC476754
0.5714	Remote Similarity	NPC473442
0.5714	Remote Similarity	NPC120167
0.5657	Remote Similarity	NPC21667
0.5652	Remote Similarity	NPC21773
0.5636	Remote Similarity	NPC176012
0.5625	Remote Similarity	NPC472856
0.5619	Remote Similarity	NPC93027

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 NPC57163 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	95
0.1-0.2	821
0.2-0.3	4637
0.3-0.4	3043
0.4-0.5	515
0.5-0.6	35
0.6-0.7	3
0.7-0.8	1
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
0.6552	Remote Similarity	NPD5365	Phase 2
0.6237	Remote Similarity	NPD529	Approved
0.6	Remote Similarity	NPD3155	Clinical (unspecified phase)
0.5644	Remote Similarity	NPD3176	Clinical (unspecified phase)

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