NPASS Compound

Structure

NPC473442 OpenBabel07101718242D 29 32 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 -3.4641 -3.0000 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 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 -2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 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 -1.7321 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2 18 1 0 0 0 0 5 27 1 0 0 0 0 6 27 1 0 0 0 0 7 28 1 0 0 0 0 8 9 1 0 0 0 0 8 19 1 0 0 0 0 10 11 1 0 0 0 0 10 22 1 0 0 0 0 11 23 1 0 0 0 0 12 14 1 0 0 0 0 12 20 1 0 0 0 0 13 15 1 0 0 0 0 13 24 1 0 0 0 0 14 25 1 0 0 0 0 15 26 1 0 0 0 0 16 19 1 0 0 0 0 16 20 1 0 0 0 0 17 1 1 1 0 0 0 17 22 1 0 0 0 0 17 27 1 0 0 0 0 18 28 1 0 0 0 0 18 29 2 0 0 0 0 19 25 1 1 0 0 0 20 28 1 1 0 0 0 21 9 1 6 0 0 0 21 23 1 0 0 0 0 21 24 1 0 0 0 0 22 26 1 1 0 0 0 23 26 1 1 0 0 0 24 25 1 1 0 0 0 25 3 1 1 0 0 0 26 4 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	402.36
Volume:	452.174
LogP:	5.55
LogD:	4.448
LogS:	-3.202
# Rotatable Bonds:	4
TPSA:	23.55
# H-Bond Aceptor:	3
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.627
Synthetic Accessibility Score:	4.454
Fsp3:	0.962
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:	-4.71
MDCK Permeability:	1.0799327355925925e-05
Pgp-inhibitor:	0.998
Pgp-substrate:	0.664
Human Intestinal Absorption (HIA):	0.009
20% Bioavailability (F20%):	0.136
30% Bioavailability (F30%):	0.18

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.259
Plasma Protein Binding (PPB):	63.51799011230469%
Volume Distribution (VD):	0.987
Pgp-substrate:	30.135038375854492%

ADMET: Metabolism

CYP1A2-inhibitor:	0.045
CYP1A2-substrate:	0.259
CYP2C19-inhibitor:	0.036
CYP2C19-substrate:	0.971
CYP2C9-inhibitor:	0.03
CYP2C9-substrate:	0.062
CYP2D6-inhibitor:	0.333
CYP2D6-substrate:	0.874
CYP3A4-inhibitor:	0.808
CYP3A4-substrate:	0.908

ADMET: Excretion

Clearance (CL):	12.979
Half-life (T1/2):	0.122

ADMET: Toxicity

hERG Blockers:	0.643
Human Hepatotoxicity (H-HT):	0.462
Drug-inuced Liver Injury (DILI):	0.892
AMES Toxicity:	0.17
Rat Oral Acute Toxicity:	0.743
Maximum Recommended Daily Dose:	0.31
Skin Sensitization:	0.966
Carcinogencity:	0.55
Eye Corrosion:	0.98
Eye Irritation:	0.149
Respiratory Toxicity:	0.946

Download Data

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

Natural Product: NPC473442

Natural Product ID:	NPC473442
*Common Name:**	N-[(3S,5S,8R,9S,10S,13S,14S,17S)-17-((S)-1-Dimethylamino-Ethyl)-10,13-Dimethyl-Hexadecahydro-Cyclopenta[A]Phenanthren-3-Yl]-N-Methyl-Acetamide
IUPAC Name:	N-[(3S,5S,8R,9S,10S,13S,14S,17S)-17-[(1S)-1-(dimethylamino)ethyl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]-N-methylacetamide
Synonyms:
Standard InCHIKey:	WDKKOVABYKVZIW-VCJWWASDSA-N
Standard InCHI:	InChI=1S/C26H46N2O/c1-17(27(5)6)22-10-11-23-21-9-8-19-16-20(28(7)18(2)29)12-14-25(19,3)24(21)13-15-26(22,23)4/h17,19-24H,8-16H2,1-7H3/t17-,19-,20-,21-,22+,23-,24-,25-,26+/m0/s1
SMILES:	CN([C@H]([C@H]1CC[C@@H]2[C@]1(C)CC[C@H]1[C@H]2CC[C@@H]2[C@]1(C)CC[C@@H](C2)N(C(=O)C)C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL434042
PubChem CID:	44358214
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
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14584959]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14643329]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9548847]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO27888	Sarcococca saligna	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27888	Sarcococca saligna	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	1

Activity Type	# Activity
Individual Protein	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT204	Individual Protein	Acetylcholinesterase	Homo sapiens	IC50	=	70794.58	nM	PMID[534618]

☑ 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 NPC473442 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	233
0.1-0.2	16950
0.2-0.3	14510
0.3-0.4	8528
0.4-0.5	2053
0.5-0.6	335
0.6-0.7	69
0.7-0.8	9
0.8-0.85	5
0.85-0.9	2
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC120167
0.9286	High Similarity	NPC25110
0.8667	High Similarity	NPC90150
0.8462	Intermediate Similarity	NPC21781
0.8228	Intermediate Similarity	NPC34811
0.8228	Intermediate Similarity	NPC147513
0.8169	Intermediate Similarity	NPC245223
0.8077	Intermediate Similarity	NPC215474
0.8025	Intermediate Similarity	NPC43308
0.7971	Intermediate Similarity	NPC53276
0.7917	Intermediate Similarity	NPC124384
0.7901	Intermediate Similarity	NPC157479
0.7857	Intermediate Similarity	NPC469970
0.7534	Intermediate Similarity	NPC271640
0.7237	Intermediate Similarity	NPC110615
0.7222	Intermediate Similarity	NPC292819
0.7073	Intermediate Similarity	NPC257962
0.6915	Remote Similarity	NPC470592
0.6849	Remote Similarity	NPC477740
0.6835	Remote Similarity	NPC476904
0.6795	Remote Similarity	NPC21773
0.6771	Remote Similarity	NPC470596
0.6765	Remote Similarity	NPC472828
0.6744	Remote Similarity	NPC311769
0.6744	Remote Similarity	NPC152684
0.6744	Remote Similarity	NPC182106
0.6667	Remote Similarity	NPC7214
0.6566	Remote Similarity	NPC470595
0.6517	Remote Similarity	NPC259252
0.6506	Remote Similarity	NPC39308
0.6471	Remote Similarity	NPC109533
0.6458	Remote Similarity	NPC474001
0.6429	Remote Similarity	NPC211322
0.6404	Remote Similarity	NPC21035
0.64	Remote Similarity	NPC474027
0.64	Remote Similarity	NPC474435
0.6375	Remote Similarity	NPC265789
0.6374	Remote Similarity	NPC312637
0.6324	Remote Similarity	NPC201713
0.6322	Remote Similarity	NPC171639
0.6279	Remote Similarity	NPC329782
0.6279	Remote Similarity	NPC118329
0.6279	Remote Similarity	NPC152039
0.6264	Remote Similarity	NPC323156
0.6207	Remote Similarity	NPC472312
0.6163	Remote Similarity	NPC12035
0.6145	Remote Similarity	NPC125828
0.6143	Remote Similarity	NPC212905
0.6132	Remote Similarity	NPC246904
0.6111	Remote Similarity	NPC184819
0.6082	Remote Similarity	NPC140685
0.6075	Remote Similarity	NPC473573
0.6064	Remote Similarity	NPC93027
0.6064	Remote Similarity	NPC476753
0.6064	Remote Similarity	NPC476752
0.6061	Remote Similarity	NPC58200
0.6053	Remote Similarity	NPC477739
0.6027	Remote Similarity	NPC143597
0.6027	Remote Similarity	NPC151464
0.6	Remote Similarity	NPC75810
0.6	Remote Similarity	NPC476288
0.6	Remote Similarity	NPC476754
0.5979	Remote Similarity	NPC473537
0.5974	Remote Similarity	NPC89921
0.5955	Remote Similarity	NPC21667
0.5938	Remote Similarity	NPC174117
0.5934	Remote Similarity	NPC166458
0.5918	Remote Similarity	NPC252564
0.5918	Remote Similarity	NPC475249
0.5918	Remote Similarity	NPC220111
0.5914	Remote Similarity	NPC135005
0.5909	Remote Similarity	NPC470594
0.5909	Remote Similarity	NPC470593
0.5909	Remote Similarity	NPC474122
0.59	Remote Similarity	NPC476755
0.5882	Remote Similarity	NPC36497
0.5876	Remote Similarity	NPC476903
0.5859	Remote Similarity	NPC201712
0.5816	Remote Similarity	NPC184033
0.5811	Remote Similarity	NPC474105
0.5806	Remote Similarity	NPC237535
0.58	Remote Similarity	NPC475518
0.5784	Remote Similarity	NPC476921
0.5769	Remote Similarity	NPC475755
0.5753	Remote Similarity	NPC288296
0.5753	Remote Similarity	NPC53245
0.5743	Remote Similarity	NPC152718
0.5732	Remote Similarity	NPC266383
0.5732	Remote Similarity	NPC206241
0.5732	Remote Similarity	NPC290231
0.5732	Remote Similarity	NPC68043
0.5732	Remote Similarity	NPC48448
0.5732	Remote Similarity	NPC271803
0.5732	Remote Similarity	NPC180401
0.573	Remote Similarity	NPC192456
0.5728	Remote Similarity	NPC86906
0.5714	Remote Similarity	NPC116881
0.5714	Remote Similarity	NPC57163
0.5714	Remote Similarity	NPC473994
0.566	Remote Similarity	NPC63511
0.5658	Remote Similarity	NPC324944
0.5652	Remote Similarity	NPC24733
0.5644	Remote Similarity	NPC476922
0.5619	Remote Similarity	NPC476918
0.5616	Remote Similarity	NPC475272

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 NPC473442 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	127
0.1-0.2	2714
0.2-0.3	4684
0.3-0.4	1319
0.4-0.5	214
0.5-0.6	80
0.6-0.7	9
0.7-0.8	2
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.84	Intermediate Similarity	NPD7155	Clinical (unspecified phase)
0.7529	Intermediate Similarity	NPD6934	Discontinued
0.6429	Remote Similarity	NPD3727	Discontinued
0.6353	Remote Similarity	NPD3155	Clinical (unspecified phase)
0.6324	Remote Similarity	NPD4834	Discontinued
0.6029	Remote Similarity	NPD5379	Clinical (unspecified phase)
0.6	Remote Similarity	NPD7911	Approved
0.6	Remote Similarity	NPD7986	Approved
0.6	Remote Similarity	NPD7987	Approved
0.6	Remote Similarity	NPD7912	Approved
0.6	Remote Similarity	NPD5793	Discontinued
0.5979	Remote Similarity	NPD7919	Phase 3
0.5979	Remote Similarity	NPD7920	Phase 3
0.5934	Remote Similarity	NPD8308	Discontinued
0.5918	Remote Similarity	NPD8088	Phase 1
0.5882	Remote Similarity	NPD6920	Discontinued
0.5882	Remote Similarity	NPD8040	Discontinued
0.5825	Remote Similarity	NPD7990	Approved
0.5825	Remote Similarity	NPD7989	Approved
0.5825	Remote Similarity	NPD7646	Clinical (unspecified phase)
0.5769	Remote Similarity	NPD6415	Discontinued
0.5747	Remote Similarity	NPD4776	Phase 2
0.5747	Remote Similarity	NPD4777	Suspended
0.5694	Remote Similarity	NPD3721	Approved
0.5694	Remote Similarity	NPD3722	Approved
0.567	Remote Similarity	NPD5769	Clinical (unspecified phase)
0.5652	Remote Similarity	NPD872	Approved
0.5652	Remote Similarity	NPD874	Approved
0.5648	Remote Similarity	NPD8298	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