NPASS Compound

Structure

NPC21781 OpenBabel07101719512D 27 30 0 0 1 0 0 0 0 0999 V2000 -4.8363 -2.9680 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 -2.1913 -2.4135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4980 -4.4543 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2109 -3.2953 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 1.0000 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 -0.8660 1.5000 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 -4.1369 -1.0000 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 1.7321 -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 0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -2.0000 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 -3.8581 -2.7601 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5491 -1.8090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5981 -0.5000 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 0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1890 -3.5032 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4 26 1 0 0 0 0 5 26 1 0 0 0 0 6 27 1 0 0 0 0 7 27 1 0 0 0 0 8 9 1 0 0 0 0 8 18 1 0 0 0 0 10 11 1 0 0 0 0 10 21 1 0 0 0 0 11 22 1 0 0 0 0 12 14 1 0 0 0 0 12 19 1 0 0 0 0 13 15 1 0 0 0 0 13 23 1 0 0 0 0 14 24 1 0 0 0 0 15 25 1 0 0 0 0 16 18 1 0 0 0 0 16 19 1 0 0 0 0 17 1 1 1 0 0 0 17 21 1 0 0 0 0 17 26 1 0 0 0 0 18 24 1 1 0 0 0 19 27 1 1 0 0 0 20 9 1 6 0 0 0 20 22 1 0 0 0 0 20 23 1 0 0 0 0 21 25 1 1 0 0 0 22 25 1 1 0 0 0 23 24 1 1 0 0 0 24 2 1 1 0 0 0 25 3 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	374.37
Volume:	428.724
LogP:	5.856
LogD:	4.577
LogS:	-3.566
# Rotatable Bonds:	3
TPSA:	6.48
# H-Bond Aceptor:	2
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.641
Synthetic Accessibility Score:	4.386
Fsp3:	1.0
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:	-4.899
MDCK Permeability:	8.951576091931202e-06
Pgp-inhibitor:	0.996
Pgp-substrate:	0.79
Human Intestinal Absorption (HIA):	0.008
20% Bioavailability (F20%):	0.052
30% Bioavailability (F30%):	0.004

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.456
Plasma Protein Binding (PPB):	62.97142791748047%
Volume Distribution (VD):	1.972
Pgp-substrate:	37.30472183227539%

ADMET: Metabolism

CYP1A2-inhibitor:	0.087
CYP1A2-substrate:	0.125
CYP2C19-inhibitor:	0.024
CYP2C19-substrate:	0.988
CYP2C9-inhibitor:	0.028
CYP2C9-substrate:	0.117
CYP2D6-inhibitor:	0.849
CYP2D6-substrate:	0.93
CYP3A4-inhibitor:	0.572
CYP3A4-substrate:	0.896

ADMET: Excretion

Clearance (CL):	21.515
Half-life (T1/2):	0.045

ADMET: Toxicity

hERG Blockers:	0.919
Human Hepatotoxicity (H-HT):	0.406
Drug-inuced Liver Injury (DILI):	0.8
AMES Toxicity:	0.085
Rat Oral Acute Toxicity:	0.498
Maximum Recommended Daily Dose:	0.464
Skin Sensitization:	0.966
Carcinogencity:	0.551
Eye Corrosion:	1.0
Eye Irritation:	0.413
Respiratory Toxicity:	0.922

Download Data

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

Natural Product: NPC21781

Natural Product ID:	NPC21781
*Common Name:**	N-Methypachysamine A
IUPAC Name:	(3S,5S,8R,9S,10S,13S,14S,17S)-17-[(1S)-1-(dimethylamino)ethyl]-N,N,10,13-tetramethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine
Synonyms:
Standard InCHIKey:	IHGKQRLXUYWOQB-SYILLIHQSA-N
Standard InCHI:	InChI=1S/C25H46N2/c1-17(26(4)5)21-10-11-22-20-9-8-18-16-19(27(6)7)12-14-24(18,2)23(20)13-15-25(21,22)3/h17-23H,8-16H2,1-7H3/t17-,18-,19-,20-,21+,22-,23-,24-,25+/m0/s1
SMILES:	C[C@@H]([C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](CC[C@]4(C)[C@H]3CC[C@]12C)N(C)C)N(C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL496255
PubChem CID:	44587246
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0002340] Azasteroids and derivatives

*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
NPO12900	Sarcococca hookeriana	Species	Buxaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[17827771]
NPO12900	Sarcococca hookeriana	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18681480]
NPO12900	Sarcococca hookeriana	Species	Buxaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[18681480]
NPO12900	Sarcococca hookeriana	Species	Buxaceae	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
MIC	3
Others	4

Activity Type	# Activity
Individual Protein	2
Organism	7

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT204	Individual Protein	Acetylcholinesterase	Homo sapiens	IC50	=	22100.0	nM	PMID[574108]
NPT439	Individual Protein	Butyrylcholinesterase	Homo sapiens	IC50	=	1600.0	nM	PMID[574108]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	19.0	mm	PMID[574108]
NPT2921	Organism	Pseudomonas	Pseudomonas	IZ	=	14.5	mm	PMID[574108]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	83500.0	nM	PMID[574108]
NPT2921	Organism	Pseudomonas	Pseudomonas	MIC	=	167100.0	nM	PMID[574108]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	IZ	=	11.0	mm	PMID[574108]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	IZ	=	8.0	mm	PMID[574108]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	167100.0	nM	PMID[574108]

☑ 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 NPC21781 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	865
0.1-0.2	20836
0.2-0.3	12962
0.3-0.4	6423
0.4-0.5	1275
0.5-0.6	262
0.6-0.7	52
0.7-0.8	14
0.8-0.85	0
0.85-0.9	5
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9322	High Similarity	NPC53276
0.9167	High Similarity	NPC469970
0.873	High Similarity	NPC271640
0.8594	High Similarity	NPC245223
0.8594	High Similarity	NPC124384
0.8462	Intermediate Similarity	NPC473442
0.8462	Intermediate Similarity	NPC120167
0.7931	Intermediate Similarity	NPC472828
0.7857	Intermediate Similarity	NPC25110
0.7826	Intermediate Similarity	NPC476904
0.7794	Intermediate Similarity	NPC21773
0.7385	Intermediate Similarity	NPC477740
0.7361	Intermediate Similarity	NPC7214
0.7333	Intermediate Similarity	NPC257962
0.7333	Intermediate Similarity	NPC90150
0.7297	Intermediate Similarity	NPC211322
0.7286	Intermediate Similarity	NPC265789
0.7167	Intermediate Similarity	NPC212905
0.7119	Intermediate Similarity	NPC201713
0.7042	Intermediate Similarity	NPC110615
0.6986	Remote Similarity	NPC125828
0.6962	Remote Similarity	NPC147513
0.6962	Remote Similarity	NPC152684
0.6962	Remote Similarity	NPC34811
0.6923	Remote Similarity	NPC171639
0.6883	Remote Similarity	NPC329782
0.6883	Remote Similarity	NPC152039
0.6883	Remote Similarity	NPC118329
0.6795	Remote Similarity	NPC472312
0.6795	Remote Similarity	NPC215474
0.679	Remote Similarity	NPC43308
0.6753	Remote Similarity	NPC12035
0.6667	Remote Similarity	NPC157479
0.6667	Remote Similarity	NPC109533
0.6618	Remote Similarity	NPC474027
0.6618	Remote Similarity	NPC474435
0.6618	Remote Similarity	NPC475755
0.6585	Remote Similarity	NPC21035
0.6543	Remote Similarity	NPC182106
0.6543	Remote Similarity	NPC311769
0.6515	Remote Similarity	NPC324944
0.6508	Remote Similarity	NPC475272
0.6471	Remote Similarity	NPC477739
0.6456	Remote Similarity	NPC474122
0.6389	Remote Similarity	NPC476288
0.6377	Remote Similarity	NPC89921
0.6364	Remote Similarity	NPC173815
0.6341	Remote Similarity	NPC24733
0.631	Remote Similarity	NPC259252
0.6235	Remote Similarity	NPC323156
0.6212	Remote Similarity	NPC318036
0.6173	Remote Similarity	NPC283277
0.6145	Remote Similarity	NPC75810
0.6111	Remote Similarity	NPC292819
0.6071	Remote Similarity	NPC166458
0.6	Remote Similarity	NPC219621
0.6	Remote Similarity	NPC476903
0.6	Remote Similarity	NPC127944
0.5977	Remote Similarity	NPC312637
0.5934	Remote Similarity	NPC473537
0.5914	Remote Similarity	NPC474582
0.5904	Remote Similarity	NPC153734
0.589	Remote Similarity	NPC474456
0.5882	Remote Similarity	NPC56107
0.5875	Remote Similarity	NPC39308
0.587	Remote Similarity	NPC140685
0.587	Remote Similarity	NPC252564
0.587	Remote Similarity	NPC475249
0.5857	Remote Similarity	NPC317778
0.5854	Remote Similarity	NPC192456
0.5851	Remote Similarity	NPC470592
0.5843	Remote Similarity	NPC476753
0.5843	Remote Similarity	NPC476752
0.5821	Remote Similarity	NPC184819
0.5811	Remote Similarity	NPC476135
0.5806	Remote Similarity	NPC201712
0.5778	Remote Similarity	NPC476754
0.5745	Remote Similarity	NPC475518
0.5735	Remote Similarity	NPC143597
0.5735	Remote Similarity	NPC151464
0.5729	Remote Similarity	NPC470596
0.5714	Remote Similarity	NPC472827
0.5714	Remote Similarity	NPC21667
0.5714	Remote Similarity	NPC152211
0.5714	Remote Similarity	NPC28755
0.5684	Remote Similarity	NPC476755
0.5684	Remote Similarity	NPC58200
0.5682	Remote Similarity	NPC135005
0.5676	Remote Similarity	NPC37792
0.5672	Remote Similarity	NPC476676
0.567	Remote Similarity	NPC36497
0.567	Remote Similarity	NPC474695
0.5658	Remote Similarity	NPC184919
0.5658	Remote Similarity	NPC138409
0.5625	Remote Similarity	NPC476308
0.5625	Remote Similarity	NPC241879
0.5625	Remote Similarity	NPC174803
0.5625	Remote Similarity	NPC259989
0.5606	Remote Similarity	NPC151004
0.5606	Remote Similarity	NPC228980
0.5606	Remote Similarity	NPC243635

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 NPC21781 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	265
0.1-0.2	4317
0.2-0.3	3566
0.3-0.4	806
0.4-0.5	123
0.5-0.6	58
0.6-0.7	11
0.7-0.8	4
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
0.7213	Intermediate Similarity	NPD3727	Discontinued
0.7119	Intermediate Similarity	NPD4834	Discontinued
0.7067	Intermediate Similarity	NPD7155	Clinical (unspecified phase)
0.678	Remote Similarity	NPD5379	Clinical (unspecified phase)
0.6721	Remote Similarity	NPD5793	Discontinued
0.661	Remote Similarity	NPD874	Approved
0.661	Remote Similarity	NPD872	Approved
0.6353	Remote Similarity	NPD6934	Discontinued
0.6349	Remote Similarity	NPD3721	Approved
0.6349	Remote Similarity	NPD3722	Approved
0.6271	Remote Similarity	NPD871	Approved
0.6271	Remote Similarity	NPD873	Approved
0.6212	Remote Similarity	NPD625	Approved
0.6212	Remote Similarity	NPD626	Phase 3
0.6212	Remote Similarity	NPD628	Phase 3
0.6212	Remote Similarity	NPD627	Approved
0.6154	Remote Similarity	NPD3711	Phase 3
0.6154	Remote Similarity	NPD3712	Phase 3
0.5934	Remote Similarity	NPD7919	Phase 3
0.5934	Remote Similarity	NPD7920	Phase 3
0.5882	Remote Similarity	NPD8308	Discontinued
0.587	Remote Similarity	NPD8088	Phase 1
0.5763	Remote Similarity	NPD347	Approved
0.5763	Remote Similarity	NPD346	Approved
0.5714	Remote Similarity	NPD5365	Phase 2
0.5667	Remote Similarity	NPD718	Approved
0.5667	Remote Similarity	NPD390	Approved
0.5625	Remote Similarity	NPD7986	Approved
0.5625	Remote Similarity	NPD7987	Approved
0.5625	Remote Similarity	NPD7912	Approved
0.5625	Remote Similarity	NPD7911	Approved
0.5606	Remote Similarity	NPD1822	Approved
0.5606	Remote Similarity	NPD1821	Approved
0.5606	Remote Similarity	NPD1823	Approved
0.5604	Remote Similarity	NPD5771	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