NPASS Compound

Structure

NPC473695 OpenBabel07101719122D 35 38 0 0 1 0 0 0 0 0999 V2000 3.0411 -2.2352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3675 -1.7042 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5599 -2.6314 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5038 -1.0959 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9762 -2.8500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3577 -2.5565 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0590 -2.7305 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4352 -0.4764 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3531 -2.8672 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6676 -2.2280 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5105 -2.7199 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1692 0.0874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7581 -2.6811 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8172 -1.8019 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9186 -2.5267 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7346 0.5342 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2559 -2.3120 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7805 -1.3518 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2129 -2.1841 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 0.9012 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1784 0.8156 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7805 1.3518 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2689 -1.1999 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8949 -1.7041 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5610 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6784 -0.6611 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2847 -1.3036 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0993 -1.7997 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7805 -0.4506 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2346 -0.5775 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3423 -1.7515 0.0000 C 0 0 3 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 1.5610 0.9012 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -1.0498 -0.9179 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -2.2406 -1.8247 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 1 3 1 0 0 0 0 2 4 1 0 0 0 0 3 5 1 0 0 0 0 4 8 1 0 0 0 0 5 9 1 0 0 0 0 6 7 1 0 0 0 0 6 10 2 0 0 0 0 7 11 2 0 0 0 0 8 12 1 0 0 0 0 9 13 1 0 0 0 0 10 14 1 0 0 0 0 11 15 1 0 0 0 0 12 16 1 0 0 0 0 13 17 1 0 0 0 0 14 18 1 0 0 0 0 15 19 2 0 0 0 0 16 21 1 0 0 0 0 19 31 1 0 0 0 0 20 22 1 0 0 0 0 21 33 1 0 0 0 0 22 33 1 0 0 0 0 23 28 1 0 0 0 0 24 28 1 0 0 0 0 24 34 1 0 0 0 0 25 29 1 0 0 0 0 25 33 1 0 0 0 0 26 30 1 0 0 0 0 26 34 1 0 0 0 0 27 31 1 0 0 0 0 27 34 1 0 0 0 0 28 17 1 6 0 0 0 29 18 1 6 0 0 0 29 32 1 0 0 0 0 30 23 1 6 0 0 0 30 32 1 0 0 0 0 31 35 1 0 0 0 0 32 20 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	482.42
Volume:	550.677
LogP:	7.549
LogD:	5.262
LogS:	-5.111
# Rotatable Bonds:	0
TPSA:	26.71
# H-Bond Aceptor:	3
# H-Bond Donor:	1
# Rings:	5
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.403
Synthetic Accessibility Score:	6.123
Fsp3:	0.812
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.126
MDCK Permeability:	2.175546069338452e-05
Pgp-inhibitor:	0.072
Pgp-substrate:	0.982
Human Intestinal Absorption (HIA):	0.341
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	0.151

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.13
Plasma Protein Binding (PPB):	96.52350616455078%
Volume Distribution (VD):	1.794
Pgp-substrate:	2.7986156940460205%

ADMET: Metabolism

CYP1A2-inhibitor:	0.132
CYP1A2-substrate:	0.145
CYP2C19-inhibitor:	0.308
CYP2C19-substrate:	0.488
CYP2C9-inhibitor:	0.025
CYP2C9-substrate:	0.015
CYP2D6-inhibitor:	0.994
CYP2D6-substrate:	0.565
CYP3A4-inhibitor:	0.838
CYP3A4-substrate:	0.303

ADMET: Excretion

Clearance (CL):	10.772
Half-life (T1/2):	0.063

ADMET: Toxicity

hERG Blockers:	0.945
Human Hepatotoxicity (H-HT):	0.988
Drug-inuced Liver Injury (DILI):	0.912
AMES Toxicity:	0.061
Rat Oral Acute Toxicity:	0.078
Maximum Recommended Daily Dose:	0.903
Skin Sensitization:	0.976
Carcinogencity:	0.064
Eye Corrosion:	0.011
Eye Irritation:	0.041
Respiratory Toxicity:	0.875

Download Data

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

Natural Product: NPC473695

Natural Product ID:	NPC473695
*Common Name:**	Arenosclerin E
IUPAC Name:	n.a.
Synonyms:	Arenosclerin E
Standard InCHIKey:	FWLQTNCVIRJADS-IPHCVPHUSA-N
Standard InCHI:	InChI=1S/C32H54N2O/c35-31-19-15-11-7-6-10-14-18-29-25-33-21-16-12-8-4-2-1-3-5-9-13-17-28-23-30(32(29)20-22-33)26-34(24-28)27-31/h6-7,10-11,15,19,28-32,35H,1-5,8-9,12-14,16-18,20-27H2/b10-6-,11-7-,19-15-/t28-,29-,30+,31?,32+/m0/s1
SMILES:	OC1/C=CC=C/C=CCC[C@@H]2[C@@H]3[C@H]4CN(C1)C[C@@H](CCCCCCCCCCCCN(CC3)C2)C4
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL449410
PubChem CID:	44421344
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000195] Piperidines

*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
NPO6365	Pachychalina alcaloidifera	Species	Niphatidae	Eukaryota	n.a.	Brazilian	n.a.	PMID[17346073]
NPO6365	Pachychalina alcaloidifera	Species	Niphatidae	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
Others	3

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell Line	HL-60	Homo sapiens	Activity	=	6.9	ug/ml	Open TG-GATES in vivo data: Hematology
NPT180	Cell Line	HCT-8	Homo sapiens	Activity	>	25	ug/ml	PMID[17253840]
NPT399	Cell Line	SF-295	Homo sapiens	Activity	=	8.7	ug/ml	PMID[17253840]

☑ 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 NPC473695 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	73
0.1-0.2	783
0.2-0.3	14693
0.3-0.4	19119
0.4-0.5	6977
0.5-0.6	993
0.6-0.7	52
0.7-0.8	5
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	NPC473446
0.9211	High Similarity	NPC476560
0.7639	Intermediate Similarity	NPC82919
0.75	Intermediate Similarity	NPC231129
0.7237	Intermediate Similarity	NPC476559
0.7216	Intermediate Similarity	NPC473254
0.6875	Remote Similarity	NPC23721
0.6842	Remote Similarity	NPC470382
0.6842	Remote Similarity	NPC476261
0.6842	Remote Similarity	NPC471635
0.6842	Remote Similarity	NPC119225
0.6842	Remote Similarity	NPC25033
0.6667	Remote Similarity	NPC100810
0.6667	Remote Similarity	NPC144714
0.6471	Remote Similarity	NPC470993
0.6471	Remote Similarity	NPC470992
0.6408	Remote Similarity	NPC472856
0.6404	Remote Similarity	NPC209232
0.6364	Remote Similarity	NPC473972
0.6364	Remote Similarity	NPC91036
0.6364	Remote Similarity	NPC473971
0.6364	Remote Similarity	NPC475363
0.6353	Remote Similarity	NPC26932
0.6279	Remote Similarity	NPC473588
0.6279	Remote Similarity	NPC78562
0.6263	Remote Similarity	NPC475503
0.6211	Remote Similarity	NPC316186
0.62	Remote Similarity	NPC475646
0.6154	Remote Similarity	NPC477001
0.6154	Remote Similarity	NPC477000
0.6104	Remote Similarity	NPC473865
0.6104	Remote Similarity	NPC474643
0.61	Remote Similarity	NPC476903
0.6067	Remote Similarity	NPC308050
0.6049	Remote Similarity	NPC472544
0.6023	Remote Similarity	NPC34672
0.6023	Remote Similarity	NPC313179
0.6023	Remote Similarity	NPC69383
0.6023	Remote Similarity	NPC171148
0.602	Remote Similarity	NPC145707
0.6	Remote Similarity	NPC311164
0.6	Remote Similarity	NPC272732
0.5974	Remote Similarity	NPC329686
0.5974	Remote Similarity	NPC474644
0.5962	Remote Similarity	NPC247060
0.5962	Remote Similarity	NPC50815
0.5962	Remote Similarity	NPC471083
0.5962	Remote Similarity	NPC473289
0.5957	Remote Similarity	NPC234822
0.5957	Remote Similarity	NPC78058
0.5957	Remote Similarity	NPC135639
0.5957	Remote Similarity	NPC143344
0.5957	Remote Similarity	NPC61321
0.5949	Remote Similarity	NPC181872
0.5946	Remote Similarity	NPC182102
0.5946	Remote Similarity	NPC26960
0.5934	Remote Similarity	NPC120699
0.5934	Remote Similarity	NPC127430
0.5909	Remote Similarity	NPC314550
0.5909	Remote Similarity	NPC470994
0.5904	Remote Similarity	NPC308844
0.5897	Remote Similarity	NPC249645
0.5897	Remote Similarity	NPC24216
0.5897	Remote Similarity	NPC306420
0.5897	Remote Similarity	NPC104138
0.5897	Remote Similarity	NPC55412
0.5897	Remote Similarity	NPC261158
0.5875	Remote Similarity	NPC312826
0.5854	Remote Similarity	NPC477106
0.5833	Remote Similarity	NPC166458
0.5833	Remote Similarity	NPC159367
0.5825	Remote Similarity	NPC91604
0.5825	Remote Similarity	NPC270813
0.5823	Remote Similarity	NPC11130
0.5802	Remote Similarity	NPC130807
0.5802	Remote Similarity	NPC176621
0.5795	Remote Similarity	NPC130665
0.5794	Remote Similarity	NPC55462
0.5789	Remote Similarity	NPC475975
0.5784	Remote Similarity	NPC289140
0.5783	Remote Similarity	NPC206660
0.5769	Remote Similarity	NPC297020
0.5769	Remote Similarity	NPC471992
0.5769	Remote Similarity	NPC273023
0.5761	Remote Similarity	NPC90839
0.5755	Remote Similarity	NPC241879
0.5752	Remote Similarity	NPC288629
0.5747	Remote Similarity	NPC472543
0.5745	Remote Similarity	NPC477385
0.5745	Remote Similarity	NPC224072
0.5745	Remote Similarity	NPC477390
0.5741	Remote Similarity	NPC315426
0.5732	Remote Similarity	NPC225342
0.5732	Remote Similarity	NPC469728
0.5729	Remote Similarity	NPC152684
0.5728	Remote Similarity	NPC474164
0.5727	Remote Similarity	NPC65855
0.5727	Remote Similarity	NPC292758
0.5714	Remote Similarity	NPC77703
0.5714	Remote Similarity	NPC477525
0.5714	Remote Similarity	NPC118275
0.5714	Remote Similarity	NPC478137
0.5701	Remote Similarity	NPC75523
0.5686	Remote Similarity	NPC469739
0.5679	Remote Similarity	NPC122239
0.5679	Remote Similarity	NPC475931
0.5667	Remote Similarity	NPC63284
0.5663	Remote Similarity	NPC471023
0.5663	Remote Similarity	NPC55068
0.5641	Remote Similarity	NPC315188
0.5638	Remote Similarity	NPC82799
0.5632	Remote Similarity	NPC471560
0.5632	Remote Similarity	NPC103712
0.5632	Remote Similarity	NPC291196
0.5625	Remote Similarity	NPC477199
0.5625	Remote Similarity	NPC207048
0.5619	Remote Similarity	NPC135799
0.5612	Remote Similarity	NPC324506
0.561	Remote Similarity	NPC112398
0.561	Remote Similarity	NPC471081
0.5607	Remote Similarity	NPC55336
0.5604	Remote Similarity	NPC259989
0.5604	Remote Similarity	NPC320667
0.5604	Remote Similarity	NPC174803
0.5604	Remote Similarity	NPC214125

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 NPC473695 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	83
0.1-0.2	433
0.2-0.3	3610
0.3-0.4	3656
0.4-0.5	1215
0.5-0.6	150
0.6-0.7	3
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
0.6139	Remote Similarity	NPD4813	Approved
0.6139	Remote Similarity	NPD4263	Approved
0.6095	Remote Similarity	NPD7333	Discontinued
0.6023	Remote Similarity	NPD8264	Approved
0.5981	Remote Similarity	NPD4095	Clinical (unspecified phase)
0.5963	Remote Similarity	NPD4253	Approved
0.5963	Remote Similarity	NPD4254	Approved
0.5897	Remote Similarity	NPD4219	Approved
0.5818	Remote Similarity	NPD4025	Clinical (unspecified phase)
0.5755	Remote Similarity	NPD3681	Approved
0.5755	Remote Similarity	NPD4231	Approved
0.5755	Remote Similarity	NPD3683	Approved
0.5755	Remote Similarity	NPD4229	Approved
0.5739	Remote Similarity	NPD7522	Discontinued
0.5726	Remote Similarity	NPD7725	Approved
0.5663	Remote Similarity	NPD3210	Clinical (unspecified phase)
0.566	Remote Similarity	NPD4817	Approved
0.566	Remote Similarity	NPD855	Approved
0.566	Remote Similarity	NPD854	Approved
0.566	Remote Similarity	NPD4818	Approved
0.5652	Remote Similarity	NPD7322	Clinical (unspecified phase)
0.5631	Remote Similarity	NPD5349	Clinical (unspecified phase)
0.5607	Remote Similarity	NPD4658	Approved
0.5607	Remote Similarity	NPD4656	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