NPASS Compound

Structure

NPC208657 OpenBabel07101718202D 26 26 0 0 1 0 0 0 0 0999 V2000 7.7942 5.5000 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 -2.5981 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 5.5000 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 5.1962 6.0000 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 5.1962 7.0000 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 6.0622 7.5000 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 6.9282 7.0000 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 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 2 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 0.8660 -0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 2 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 6.0622 5.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 18 1 0 0 0 0 3 20 1 0 0 0 0 4 5 1 0 0 0 0 4 6 1 0 0 0 0 5 7 1 0 0 0 0 6 8 1 0 0 0 0 7 9 1 0 0 0 0 8 10 1 0 0 0 0 9 11 1 0 0 0 0 10 12 1 0 0 0 0 11 13 1 0 0 0 0 12 14 1 0 0 0 0 13 15 1 0 0 0 0 14 18 1 0 0 0 0 16 17 1 0 0 0 0 16 21 1 0 0 0 0 17 22 1 0 0 0 0 18 24 2 0 0 0 0 19 2 1 1 0 0 0 19 22 1 0 0 0 0 19 23 1 0 0 0 0 20 25 2 0 0 0 0 20 26 1 0 0 0 0 21 15 1 1 0 0 0 21 23 1 0 0 0 0 22 26 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	367.31
Volume:	412.606
LogP:	4.507
LogD:	4.104
LogS:	-5.312
# Rotatable Bonds:	15
TPSA:	55.4
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.333
Synthetic Accessibility Score:	3.49
Fsp3:	0.909
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.831
MDCK Permeability:	2.913593198172748e-05
Pgp-inhibitor:	0.667
Pgp-substrate:	0.822
Human Intestinal Absorption (HIA):	0.124
20% Bioavailability (F20%):	0.999
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.123
Plasma Protein Binding (PPB):	90.3021011352539%
Volume Distribution (VD):	0.924
Pgp-substrate:	4.709624290466309%

ADMET: Metabolism

CYP1A2-inhibitor:	0.182
CYP1A2-substrate:	0.499
CYP2C19-inhibitor:	0.357
CYP2C19-substrate:	0.084
CYP2C9-inhibitor:	0.114
CYP2C9-substrate:	0.5
CYP2D6-inhibitor:	0.966
CYP2D6-substrate:	0.87
CYP3A4-inhibitor:	0.547
CYP3A4-substrate:	0.156

ADMET: Excretion

Clearance (CL):	2.175
Half-life (T1/2):	0.225

ADMET: Toxicity

hERG Blockers:	0.111
Human Hepatotoxicity (H-HT):	0.949
Drug-inuced Liver Injury (DILI):	0.83
AMES Toxicity:	0.008
Rat Oral Acute Toxicity:	0.009
Maximum Recommended Daily Dose:	0.786
Skin Sensitization:	0.955
Carcinogencity:	0.06
Eye Corrosion:	0.089
Eye Irritation:	0.081
Respiratory Toxicity:	0.932

Download Data

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

Natural Product: NPC208657

Natural Product ID:	NPC208657
*Common Name:**	(-)-3-O-Acetylspectaline
IUPAC Name:	[(2R,3R,6S)-2-methyl-6-(13-oxotetradecyl)piperidin-3-yl] acetate
Synonyms:
Standard InCHIKey:	LRKWDKCSHJWJST-BAGYTPMASA-N
Standard InCHI:	InChI=1S/C22H41NO3/c1-18(24)14-12-10-8-6-4-5-7-9-11-13-15-21-16-17-22(19(2)23-21)26-20(3)25/h19,21-23H,4-17H2,1-3H3/t19-,21+,22-/m1/s1
SMILES:	CC(=O)CCCCCCCCCCCC[C@H]1CC[C@H]([C@H](N1)C)OC(=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL251644
PubChem CID:	10474155
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids 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
NPO32445	cassia spectabilis	Species	Fabaceae	Eukaryota	flowers and green fruits	n.a.	n.a.	PMID[15165164]
NPO32445	cassia spectabilis	Species	Fabaceae	Eukaryota	green fruits	n.a.	n.a.	PMID[18047293]
NPO22441	Senna spectabilis	Species	Fabaceae	Eukaryota	flowers	n.a.	n.a.	PMID[30413343]
NPO22441	Senna spectabilis	Species	Fabaceae	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
Others	9

Activity Type	# Activity
Cell Line	1
Individual Protein	1
Organism	4
Others	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT324	Individual Protein	Cyclooxygenase-1	Ovis aries	Inhibition	=	58.0	%	PMID[485029]
NPT189	Cell Line	Vero	Chlorocebus aethiops	CC50	=	254.96	ug.mL-1	PMID[485031]
NPT35	Others	n.a.		deltaA	<	10.0	%	PMID[485029]
NPT2	Others	Unspecified		Inhibition	=	75.0	%	PMID[485029]
NPT2	Others	Unspecified		Inhibition	=	50.0	%	PMID[485029]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	=	150.0	ug ml-1	PMID[485030]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	=	26.0	ug ml-1	PMID[485030]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	=	32.0	ug ml-1	PMID[485030]
NPT634	Organism	Leishmania amazonensis	Leishmania amazonensis	IC50	=	25.95	ug.mL-1	PMID[485031]
NPT2	Others	Unspecified		Ratio CC50/IC50	=	0.99	n.a.	PMID[485031]

☑ 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 NPC208657 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	121
0.1-0.2	7224
0.2-0.3	21824
0.3-0.4	11306
0.4-0.5	1816
0.5-0.6	356
0.6-0.7	42
0.7-0.8	4
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.8592	High Similarity	NPC306973
0.7397	Intermediate Similarity	NPC322319
0.7397	Intermediate Similarity	NPC326651
0.7397	Intermediate Similarity	NPC325117
0.6974	Remote Similarity	NPC107224
0.6806	Remote Similarity	NPC268927
0.6806	Remote Similarity	NPC64250
0.6806	Remote Similarity	NPC319991
0.6806	Remote Similarity	NPC276928
0.6709	Remote Similarity	NPC476694
0.6709	Remote Similarity	NPC476695
0.6709	Remote Similarity	NPC476696
0.6625	Remote Similarity	NPC185084
0.6477	Remote Similarity	NPC253975
0.6477	Remote Similarity	NPC125253
0.6477	Remote Similarity	NPC192025
0.6456	Remote Similarity	NPC268922
0.6404	Remote Similarity	NPC83839
0.6386	Remote Similarity	NPC477002
0.6364	Remote Similarity	NPC472609
0.6354	Remote Similarity	NPC472736
0.6329	Remote Similarity	NPC471418
0.6301	Remote Similarity	NPC278209
0.6277	Remote Similarity	NPC469998
0.6265	Remote Similarity	NPC470994
0.625	Remote Similarity	NPC320663
0.625	Remote Similarity	NPC224700
0.6235	Remote Similarity	NPC473741
0.6235	Remote Similarity	NPC477145
0.6207	Remote Similarity	NPC219340
0.6143	Remote Similarity	NPC50457
0.6119	Remote Similarity	NPC47363
0.6119	Remote Similarity	NPC287231
0.6098	Remote Similarity	NPC324165
0.6098	Remote Similarity	NPC169976
0.6098	Remote Similarity	NPC114640
0.6098	Remote Similarity	NPC126366
0.6098	Remote Similarity	NPC170963
0.6098	Remote Similarity	NPC33267
0.6092	Remote Similarity	NPC216090
0.6076	Remote Similarity	NPC286851
0.6076	Remote Similarity	NPC303798
0.6071	Remote Similarity	NPC474467
0.6024	Remote Similarity	NPC477643
0.6024	Remote Similarity	NPC320865
0.6024	Remote Similarity	NPC54460
0.6024	Remote Similarity	NPC477641
0.6022	Remote Similarity	NPC322966
0.6	Remote Similarity	NPC320936
0.6	Remote Similarity	NPC204709
0.598	Remote Similarity	NPC477001
0.598	Remote Similarity	NPC477000
0.5979	Remote Similarity	NPC174117
0.5972	Remote Similarity	NPC474322
0.5972	Remote Similarity	NPC123814
0.5955	Remote Similarity	NPC271772
0.5955	Remote Similarity	NPC36927
0.5949	Remote Similarity	NPC471892
0.5949	Remote Similarity	NPC142290
0.5949	Remote Similarity	NPC223386
0.5949	Remote Similarity	NPC471780
0.5949	Remote Similarity	NPC75435
0.5949	Remote Similarity	NPC198341
0.5942	Remote Similarity	NPC326957
0.5934	Remote Similarity	NPC277918
0.5921	Remote Similarity	NPC290106
0.5921	Remote Similarity	NPC76726
0.5921	Remote Similarity	NPC193593
0.5921	Remote Similarity	NPC143809
0.5921	Remote Similarity	NPC471421
0.5921	Remote Similarity	NPC233364
0.5918	Remote Similarity	NPC471843
0.5905	Remote Similarity	NPC469389
0.5905	Remote Similarity	NPC469388
0.5905	Remote Similarity	NPC472737
0.5897	Remote Similarity	NPC17455
0.5854	Remote Similarity	NPC474812
0.5844	Remote Similarity	NPC68974
0.5833	Remote Similarity	NPC248956
0.5821	Remote Similarity	NPC236579
0.5821	Remote Similarity	NPC203531
0.5802	Remote Similarity	NPC196359
0.5802	Remote Similarity	NPC78312
0.5802	Remote Similarity	NPC135539
0.5802	Remote Similarity	NPC221764
0.5789	Remote Similarity	NPC176164
0.5789	Remote Similarity	NPC189301
0.5784	Remote Similarity	NPC287638
0.5784	Remote Similarity	NPC194750
0.5784	Remote Similarity	NPC233274
0.5783	Remote Similarity	NPC477642
0.5765	Remote Similarity	NPC178919
0.5765	Remote Similarity	NPC263281
0.5753	Remote Similarity	NPC35816
0.5753	Remote Similarity	NPC325180
0.573	Remote Similarity	NPC70574
0.5729	Remote Similarity	NPC476019
0.5714	Remote Similarity	NPC254541
0.5714	Remote Similarity	NPC47135
0.5699	Remote Similarity	NPC469363
0.5696	Remote Similarity	NPC22774
0.5696	Remote Similarity	NPC2432
0.5696	Remote Similarity	NPC306462
0.5696	Remote Similarity	NPC69669
0.5696	Remote Similarity	NPC218150
0.5696	Remote Similarity	NPC150680
0.5694	Remote Similarity	NPC55678
0.5684	Remote Similarity	NPC292345
0.5667	Remote Similarity	NPC471420
0.5663	Remote Similarity	NPC28348
0.5663	Remote Similarity	NPC475808
0.5663	Remote Similarity	NPC473985
0.5663	Remote Similarity	NPC474299
0.5663	Remote Similarity	NPC474298
0.566	Remote Similarity	NPC15413
0.5658	Remote Similarity	NPC8979
0.5647	Remote Similarity	NPC474468
0.5638	Remote Similarity	NPC306838
0.5634	Remote Similarity	NPC29222
0.5634	Remote Similarity	NPC96966
0.5634	Remote Similarity	NPC121062
0.5634	Remote Similarity	NPC106872
0.5625	Remote Similarity	NPC471419
0.5625	Remote Similarity	NPC163134
0.5619	Remote Similarity	NPC195841
0.5619	Remote Similarity	NPC233256
0.5618	Remote Similarity	NPC473984
0.5618	Remote Similarity	NPC473971
0.5618	Remote Similarity	NPC98750
0.5618	Remote Similarity	NPC475363
0.5618	Remote Similarity	NPC473972
0.5616	Remote Similarity	NPC287811

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 NPC208657 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	80
0.1-0.2	1992
0.2-0.3	4818
0.3-0.4	1647
0.4-0.5	478
0.5-0.6	121
0.6-0.7	14
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
0.7051	Intermediate Similarity	NPD6704	Discontinued
0.7013	Intermediate Similarity	NPD2694	Approved
0.7013	Intermediate Similarity	NPD2697	Approved
0.7013	Intermediate Similarity	NPD2695	Approved
0.7013	Intermediate Similarity	NPD2696	Approved
0.68	Remote Similarity	NPD9648	Approved
0.6711	Remote Similarity	NPD9442	Clinical (unspecified phase)
0.6437	Remote Similarity	NPD883	Phase 2
0.6437	Remote Similarity	NPD882	Phase 2
0.6375	Remote Similarity	NPD3726	Approved
0.6375	Remote Similarity	NPD3725	Approved
0.6354	Remote Similarity	NPD3714	Approved
0.6354	Remote Similarity	NPD3713	Approved
0.6354	Remote Similarity	NPD3715	Approved
0.625	Remote Similarity	NPD8278	Approved
0.622	Remote Similarity	NPD6944	Clinical (unspecified phase)
0.6173	Remote Similarity	NPD8277	Approved
0.617	Remote Similarity	NPD6699	Clinical (unspecified phase)
0.6163	Remote Similarity	NPD617	Approved
0.6119	Remote Similarity	NPD2699	Approved
0.6111	Remote Similarity	NPD631	Approved
0.6111	Remote Similarity	NPD630	Approved
0.6024	Remote Similarity	NPD2256	Clinical (unspecified phase)
0.5972	Remote Similarity	NPD3215	Phase 1
0.5946	Remote Similarity	NPD8347	Approved
0.5946	Remote Similarity	NPD8345	Approved
0.5946	Remote Similarity	NPD8346	Approved
0.5946	Remote Similarity	NPD4281	Clinical (unspecified phase)
0.5926	Remote Similarity	NPD9451	Clinical (unspecified phase)
0.5915	Remote Similarity	NPD3214	Discontinued
0.5914	Remote Similarity	NPD621	Discontinued
0.5897	Remote Similarity	NPD9676	Phase 3
0.5862	Remote Similarity	NPD8143	Approved
0.5862	Remote Similarity	NPD8144	Approved
0.5849	Remote Similarity	NPD8087	Discontinued
0.5806	Remote Similarity	NPD3176	Clinical (unspecified phase)
0.5802	Remote Similarity	NPD8868	Approved
0.5794	Remote Similarity	NPD2690	Discontinued
0.5775	Remote Similarity	NPD9016	Clinical (unspecified phase)
0.5765	Remote Similarity	NPD9217	Clinical (unspecified phase)
0.5758	Remote Similarity	NPD5349	Clinical (unspecified phase)
0.5753	Remote Similarity	NPD9660	Approved
0.5733	Remote Similarity	NPD6706	Discontinued
0.5729	Remote Similarity	NPD2682	Approved
0.5714	Remote Similarity	NPD7535	Discontinued
0.5714	Remote Similarity	NPD7345	Approved
0.5696	Remote Similarity	NPD3205	Discontinued
0.5696	Remote Similarity	NPD9028	Phase 2
0.5696	Remote Similarity	NPD9029	Phase 3
0.5696	Remote Similarity	NPD9027	Phase 3
0.5696	Remote Similarity	NPD9026	Phase 2
0.5684	Remote Similarity	NPD618	Clinical (unspecified phase)
0.5658	Remote Similarity	NPD6439	Phase 3
0.5634	Remote Similarity	NPD6125	Clinical (unspecified phase)
0.5631	Remote Similarity	NPD8300	Approved
0.5631	Remote Similarity	NPD8301	Approved
0.5607	Remote Similarity	NPD6941	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