NPASS Compound

Structure

NPC41838 OpenBabel07101719522D 44 46 0 0 1 0 0 0 0 0999 V2000 5.1962 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9049 -4.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7443 -1.4112 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -3.5000 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 -3.0972 0.8035 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9049 -2.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9049 -4.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0012 -0.7421 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4049 -3.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3559 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9927 -1.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4049 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -3.0000 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 -1.8171 -0.1910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3559 -0.6910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0501 -1.0511 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 -2.4049 -3.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.0000 0.0000 C 0 0 2 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 -0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8171 -1.8090 0.0000 C 0 0 2 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 -2.9927 -0.1910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4049 -2.0000 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 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8422 -2.0292 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9049 -4.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9062 0.2158 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 0.8660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4049 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3070 -0.3820 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 -1.9049 -2.8660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 10 1 0 0 0 0 2 11 1 0 0 0 0 3 12 2 0 0 0 0 4 18 1 0 0 0 0 5 18 1 0 0 0 0 6 19 1 0 0 0 0 7 31 1 0 0 0 0 8 32 1 0 0 0 0 9 33 1 0 0 0 0 10 13 1 0 0 0 0 11 14 1 0 0 0 0 12 22 1 0 0 0 0 13 23 1 0 0 0 0 14 24 1 0 0 0 0 15 16 1 0 0 0 0 15 21 1 0 0 0 0 16 32 1 0 0 0 0 17 31 1 0 0 0 0 19 34 2 0 0 0 0 19 40 1 0 0 0 0 20 17 1 6 0 0 0 20 27 1 0 0 0 0 20 41 1 0 0 0 0 21 31 1 6 0 0 0 21 42 1 0 0 0 0 22 35 2 0 0 0 0 22 42 1 0 0 0 0 23 36 2 0 0 0 0 23 43 1 0 0 0 0 24 37 2 0 0 0 0 24 44 1 0 0 0 0 25 18 1 6 0 0 0 25 26 1 0 0 0 0 25 28 1 0 0 0 0 26 27 1 0 0 0 0 26 29 1 0 0 0 0 27 33 1 0 0 0 0 28 30 1 0 0 0 0 28 43 1 0 0 0 0 29 32 1 0 0 0 0 29 41 1 0 0 0 0 30 33 1 0 0 0 0 30 40 1 0 0 0 0 31 38 1 0 0 0 0 32 44 1 0 0 0 0 33 39 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	624.35
Volume:	637.165
LogP:	4.326
LogD:	2.971
LogS:	-3.886
# Rotatable Bonds:	14
TPSA:	154.89
# H-Bond Aceptor:	11
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.207
Synthetic Accessibility Score:	6.465
Fsp3:	0.818
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.839
MDCK Permeability:	0.00012233370216563344
Pgp-inhibitor:	0.998
Pgp-substrate:	0.008
Human Intestinal Absorption (HIA):	0.006
20% Bioavailability (F20%):	0.007
30% Bioavailability (F30%):	0.926

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.109
Plasma Protein Binding (PPB):	84.40518951416016%
Volume Distribution (VD):	1.195
Pgp-substrate:	6.949263095855713%

ADMET: Metabolism

CYP1A2-inhibitor:	0.016
CYP1A2-substrate:	0.045
CYP2C19-inhibitor:	0.027
CYP2C19-substrate:	0.344
CYP2C9-inhibitor:	0.109
CYP2C9-substrate:	0.031
CYP2D6-inhibitor:	0.015
CYP2D6-substrate:	0.028
CYP3A4-inhibitor:	0.658
CYP3A4-substrate:	0.427

ADMET: Excretion

Clearance (CL):	4.756
Half-life (T1/2):	0.849

ADMET: Toxicity

hERG Blockers:	0.117
Human Hepatotoxicity (H-HT):	0.796
Drug-inuced Liver Injury (DILI):	0.776
AMES Toxicity:	0.008
Rat Oral Acute Toxicity:	0.107
Maximum Recommended Daily Dose:	0.018
Skin Sensitization:	0.427
Carcinogencity:	0.054
Eye Corrosion:	0.012
Eye Irritation:	0.011
Respiratory Toxicity:	0.137

Download Data

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

Natural Product: NPC41838

Natural Product ID:	NPC41838
*Common Name:**	Simplexin E
IUPAC Name:	n.a.
Synonyms:	Simplexin E
Standard InCHIKey:	IAZCISKNKJSEDU-LCKUBEPHSA-N
Standard InCHI:	InChI=1S/C33H52O11/c1-10-13-23(36)43-28-25(18(4)5)26-27(33(9,39)30(28)40-19(6)34)20-17-31(7,38)21(42-22(35)12-3)15-16-32(8,29(26)41-20)44-24(37)14-11-2/h12,18,20-21,25-30,38-39H,3,10-11,13-17H2,1-2,4-9H3/t20-,21+,25-,26-,27-,28+,29-,30-,31+,32-,33+/m1/s1
SMILES:	CCCC(=O)O[C@]1(C)CC[C@H](OC(=O)C=C)[C@@](C[C@H]2O[C@@H]1[C@@H]1[C@@H](C(C)C)[C@H](OC(=O)CCC)[C@H]([C@@]([C@H]21)(C)O)OC(=O)C)(C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL554381
PubChem CID:	44179260
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002916] Eunicellane and asbestinane diterpenoids

*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
NPO6535	Klyxum simplex	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[19391605]
NPO6535	Klyxum simplex	Species	Alcyoniidae	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
ED50	4
Others	2

Activity Type	# Activity
Cell Line	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1184	Cell Line	Daoy	Homo sapiens	ED50	=	12.76	ug ml-1	PMID[542155]
NPT83	Cell Line	MCF7	Homo sapiens	ED50	=	7.19	ug ml-1	PMID[542155]
NPT165	Cell Line	HeLa	Homo sapiens	ED50	=	17.36	ug ml-1	PMID[542155]
NPT1171	Cell Line	HEp-2	Homo sapiens	ED50	=	10.72	ug ml-1	PMID[542155]
NPT113	Cell Line	RAW264.7	Mus musculus	Activity	=	4.8	%	PMID[542155]
NPT113	Cell Line	RAW264.7	Mus musculus	Activity	=	37.7	%	PMID[542155]

☑ 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 NPC41838 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	222
0.1-0.2	2007
0.2-0.3	6186
0.3-0.4	14017
0.4-0.5	9172
0.5-0.6	8374
0.6-0.7	2562
0.7-0.8	137
0.8-0.85	15
0.85-0.9	4
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8824	High Similarity	NPC119922
0.8824	High Similarity	NPC116320
0.8605	High Similarity	NPC211049
0.8478	Intermediate Similarity	NPC122057
0.8333	Intermediate Similarity	NPC228593
0.8333	Intermediate Similarity	NPC235196
0.8276	Intermediate Similarity	NPC186594
0.8256	Intermediate Similarity	NPC43463
0.8256	Intermediate Similarity	NPC252483
0.8256	Intermediate Similarity	NPC191345
0.8247	Intermediate Similarity	NPC272223
0.8172	Intermediate Similarity	NPC471378
0.8172	Intermediate Similarity	NPC312471
0.809	Intermediate Similarity	NPC216800
0.8085	Intermediate Similarity	NPC312805
0.8065	Intermediate Similarity	NPC291875
0.8023	Intermediate Similarity	NPC136424
0.7957	Intermediate Similarity	NPC75443
0.7957	Intermediate Similarity	NPC470260
0.7957	Intermediate Similarity	NPC92370
0.7931	Intermediate Similarity	NPC476719
0.7895	Intermediate Similarity	NPC91251
0.7857	Intermediate Similarity	NPC472998
0.7849	Intermediate Similarity	NPC44538
0.7822	Intermediate Similarity	NPC61442
0.7802	Intermediate Similarity	NPC127917
0.7789	Intermediate Similarity	NPC470262
0.7778	Intermediate Similarity	NPC470154
0.7755	Intermediate Similarity	NPC472996
0.7755	Intermediate Similarity	NPC472997
0.7742	Intermediate Similarity	NPC475684
0.7742	Intermediate Similarity	NPC246347
0.7723	Intermediate Similarity	NPC472552
0.7692	Intermediate Similarity	NPC477446
0.7692	Intermediate Similarity	NPC103171
0.7692	Intermediate Similarity	NPC470155
0.7692	Intermediate Similarity	NPC477447
0.7684	Intermediate Similarity	NPC161560
0.7677	Intermediate Similarity	NPC111348
0.766	Intermediate Similarity	NPC471377
0.7653	Intermediate Similarity	NPC469583
0.7647	Intermediate Similarity	NPC99510
0.7634	Intermediate Similarity	NPC471379
0.7634	Intermediate Similarity	NPC196911
0.7634	Intermediate Similarity	NPC476715
0.7634	Intermediate Similarity	NPC93616
0.7624	Intermediate Similarity	NPC308824
0.7624	Intermediate Similarity	NPC472554
0.7609	Intermediate Similarity	NPC239308
0.7582	Intermediate Similarity	NPC470156
0.7579	Intermediate Similarity	NPC476723
0.7579	Intermediate Similarity	NPC476724
0.7576	Intermediate Similarity	NPC472995
0.7576	Intermediate Similarity	NPC284518
0.7553	Intermediate Similarity	NPC279260
0.75	Intermediate Similarity	NPC477126
0.75	Intermediate Similarity	NPC470263
0.7476	Intermediate Similarity	NPC474575
0.7476	Intermediate Similarity	NPC23584
0.7476	Intermediate Similarity	NPC72842
0.7476	Intermediate Similarity	NPC156681
0.7475	Intermediate Similarity	NPC476720
0.7471	Intermediate Similarity	NPC476718
0.7453	Intermediate Similarity	NPC40728
0.7447	Intermediate Similarity	NPC476725
0.7419	Intermediate Similarity	NPC5958
0.7404	Intermediate Similarity	NPC283850
0.74	Intermediate Similarity	NPC473964
0.7396	Intermediate Similarity	NPC309656
0.7391	Intermediate Similarity	NPC118116
0.7379	Intermediate Similarity	NPC11956
0.7368	Intermediate Similarity	NPC477283
0.7358	Intermediate Similarity	NPC135015
0.7358	Intermediate Similarity	NPC217921
0.7358	Intermediate Similarity	NPC48548
0.7358	Intermediate Similarity	NPC128795
0.7353	Intermediate Similarity	NPC477656
0.7353	Intermediate Similarity	NPC188968
0.7347	Intermediate Similarity	NPC8729
0.7347	Intermediate Similarity	NPC165180
0.7339	Intermediate Similarity	NPC94509
0.7333	Intermediate Similarity	NPC470980
0.7327	Intermediate Similarity	NPC199099
0.7327	Intermediate Similarity	NPC274793
0.7327	Intermediate Similarity	NPC474395
0.7327	Intermediate Similarity	NPC473963
0.732	Intermediate Similarity	NPC59682
0.73	Intermediate Similarity	NPC259042
0.73	Intermediate Similarity	NPC157686
0.729	Intermediate Similarity	NPC475586
0.729	Intermediate Similarity	NPC316974
0.7283	Intermediate Similarity	NPC472951
0.7283	Intermediate Similarity	NPC472943
0.7282	Intermediate Similarity	NPC49532
0.7273	Intermediate Similarity	NPC475307
0.7273	Intermediate Similarity	NPC73314
0.7264	Intermediate Similarity	NPC88013
0.7264	Intermediate Similarity	NPC122816
0.7264	Intermediate Similarity	NPC125423
0.7255	Intermediate Similarity	NPC475068
0.7253	Intermediate Similarity	NPC264610
0.7248	Intermediate Similarity	NPC317460
0.7248	Intermediate Similarity	NPC470025
0.7248	Intermediate Similarity	NPC321272
0.7248	Intermediate Similarity	NPC328074
0.7245	Intermediate Similarity	NPC470114
0.7238	Intermediate Similarity	NPC475585
0.7238	Intermediate Similarity	NPC474550
0.7238	Intermediate Similarity	NPC473577
0.7232	Intermediate Similarity	NPC124676
0.7232	Intermediate Similarity	NPC146280
0.7228	Intermediate Similarity	NPC228766
0.7228	Intermediate Similarity	NPC165528
0.7228	Intermediate Similarity	NPC93245
0.7228	Intermediate Similarity	NPC129569
0.7222	Intermediate Similarity	NPC474567
0.7222	Intermediate Similarity	NPC316708
0.7216	Intermediate Similarity	NPC476435
0.7212	Intermediate Similarity	NPC470972
0.7212	Intermediate Similarity	NPC164551
0.7207	Intermediate Similarity	NPC89929
0.7207	Intermediate Similarity	NPC190185
0.7207	Intermediate Similarity	NPC213084
0.7204	Intermediate Similarity	NPC77003
0.72	Intermediate Similarity	NPC476722
0.72	Intermediate Similarity	NPC474841
0.72	Intermediate Similarity	NPC469596
0.72	Intermediate Similarity	NPC225474
0.72	Intermediate Similarity	NPC473434
0.72	Intermediate Similarity	NPC148000
0.72	Intermediate Similarity	NPC471446
0.7196	Intermediate Similarity	NPC289702
0.7196	Intermediate Similarity	NPC311223
0.7196	Intermediate Similarity	NPC88701
0.7196	Intermediate Similarity	NPC50124
0.7196	Intermediate Similarity	NPC181994
0.7196	Intermediate Similarity	NPC475263
0.7196	Intermediate Similarity	NPC208461
0.7196	Intermediate Similarity	NPC37628
0.7188	Intermediate Similarity	NPC155531
0.7188	Intermediate Similarity	NPC215968
0.7188	Intermediate Similarity	NPC476717
0.7188	Intermediate Similarity	NPC321812
0.7188	Intermediate Similarity	NPC322922
0.7184	Intermediate Similarity	NPC38855
0.7184	Intermediate Similarity	NPC271295
0.7184	Intermediate Similarity	NPC47024
0.7184	Intermediate Similarity	NPC477655
0.7182	Intermediate Similarity	NPC470027
0.7172	Intermediate Similarity	NPC208839
0.717	Intermediate Similarity	NPC51719
0.717	Intermediate Similarity	NPC475290
0.7168	Intermediate Similarity	NPC470186
0.7157	Intermediate Similarity	NPC473244
0.7156	Intermediate Similarity	NPC470026
0.7156	Intermediate Similarity	NPC17791
0.7143	Intermediate Similarity	NPC146432
0.7143	Intermediate Similarity	NPC473523
0.7143	Intermediate Similarity	NPC82876
0.7143	Intermediate Similarity	NPC470778
0.7143	Intermediate Similarity	NPC474124
0.713	Intermediate Similarity	NPC257017
0.713	Intermediate Similarity	NPC284828
0.713	Intermediate Similarity	NPC162009
0.713	Intermediate Similarity	NPC173905
0.713	Intermediate Similarity	NPC42662
0.713	Intermediate Similarity	NPC472216
0.713	Intermediate Similarity	NPC5475
0.7117	Intermediate Similarity	NPC299849
0.7115	Intermediate Similarity	NPC98225
0.7115	Intermediate Similarity	NPC11974
0.7115	Intermediate Similarity	NPC242666
0.7115	Intermediate Similarity	NPC111292
0.7113	Intermediate Similarity	NPC45833
0.7113	Intermediate Similarity	NPC62202
0.7113	Intermediate Similarity	NPC213658
0.7113	Intermediate Similarity	NPC110365
0.7103	Intermediate Similarity	NPC471205
0.7103	Intermediate Similarity	NPC187435
0.7103	Intermediate Similarity	NPC473586
0.7103	Intermediate Similarity	NPC67321
0.7103	Intermediate Similarity	NPC284732
0.7103	Intermediate Similarity	NPC78966
0.71	Intermediate Similarity	NPC110022
0.7091	Intermediate Similarity	NPC269530
0.7087	Intermediate Similarity	NPC476806
0.7087	Intermediate Similarity	NPC476807
0.7087	Intermediate Similarity	NPC107806
0.7087	Intermediate Similarity	NPC72647
0.7087	Intermediate Similarity	NPC216478
0.7079	Intermediate Similarity	NPC123122
0.7075	Intermediate Similarity	NPC146731
0.7075	Intermediate Similarity	NPC301787
0.7075	Intermediate Similarity	NPC473543
0.7071	Intermediate Similarity	NPC153853
0.7071	Intermediate Similarity	NPC475776
0.7069	Intermediate Similarity	NPC473802
0.7064	Intermediate Similarity	NPC177047
0.7064	Intermediate Similarity	NPC472215
0.7064	Intermediate Similarity	NPC475563

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 NPC41838 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	261
0.1-0.2	2701
0.2-0.3	3813
0.3-0.4	1615
0.4-0.5	487
0.5-0.6	241
0.6-0.7	32
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
0.7282	Intermediate Similarity	NPD5344	Discontinued
0.7196	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7019	Intermediate Similarity	NPD6648	Approved
0.6818	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6762	Remote Similarity	NPD4225	Approved
0.6757	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6733	Remote Similarity	NPD7838	Discovery
0.6667	Remote Similarity	NPD7532	Clinical (unspecified phase)
0.661	Remote Similarity	NPD6921	Approved
0.6604	Remote Similarity	NPD7638	Approved
0.6581	Remote Similarity	NPD7516	Approved
0.6579	Remote Similarity	NPD8133	Approved
0.6577	Remote Similarity	NPD6686	Approved
0.6542	Remote Similarity	NPD7639	Approved
0.6542	Remote Similarity	NPD7640	Approved
0.6496	Remote Similarity	NPD7327	Approved
0.6496	Remote Similarity	NPD7328	Approved
0.6486	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6486	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6471	Remote Similarity	NPD8380	Approved
0.6471	Remote Similarity	NPD8296	Approved
0.6471	Remote Similarity	NPD8379	Approved
0.6471	Remote Similarity	NPD8378	Approved
0.6471	Remote Similarity	NPD8335	Approved
0.6408	Remote Similarity	NPD46	Approved
0.6408	Remote Similarity	NPD6698	Approved
0.6387	Remote Similarity	NPD8294	Approved
0.6387	Remote Similarity	NPD8377	Approved
0.6364	Remote Similarity	NPD3669	Approved
0.6364	Remote Similarity	NPD371	Approved
0.6364	Remote Similarity	NPD3670	Clinical (unspecified phase)
0.6348	Remote Similarity	NPD8297	Approved
0.6333	Remote Similarity	NPD7503	Approved
0.6333	Remote Similarity	NPD8033	Approved
0.6296	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6271	Remote Similarity	NPD7115	Discovery
0.626	Remote Similarity	NPD7507	Approved
0.625	Remote Similarity	NPD6319	Approved
0.624	Remote Similarity	NPD7319	Approved
0.6228	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6198	Remote Similarity	NPD8513	Phase 3
0.6198	Remote Similarity	NPD8515	Approved
0.6198	Remote Similarity	NPD8516	Approved
0.6198	Remote Similarity	NPD8517	Approved
0.6182	Remote Similarity	NPD1700	Approved
0.6154	Remote Similarity	NPD4632	Approved
0.6126	Remote Similarity	NPD7632	Discontinued
0.6121	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6048	Remote Similarity	NPD7492	Approved
0.6038	Remote Similarity	NPD7983	Approved
0.6038	Remote Similarity	NPD8034	Phase 2
0.6038	Remote Similarity	NPD8035	Phase 2
0.6032	Remote Similarity	NPD7736	Approved
0.602	Remote Similarity	NPD6697	Approved
0.602	Remote Similarity	NPD6114	Approved
0.602	Remote Similarity	NPD6118	Approved
0.602	Remote Similarity	NPD6115	Approved
0.6	Remote Similarity	NPD6899	Approved
0.6	Remote Similarity	NPD6881	Approved
0.6	Remote Similarity	NPD6616	Approved
0.5984	Remote Similarity	NPD6054	Approved
0.5983	Remote Similarity	NPD8130	Phase 1
0.5983	Remote Similarity	NPD6650	Approved
0.5983	Remote Similarity	NPD6649	Approved
0.5952	Remote Similarity	NPD8074	Phase 3
0.5952	Remote Similarity	NPD7078	Approved
0.5932	Remote Similarity	NPD6882	Approved
0.5926	Remote Similarity	NPD7748	Approved
0.5922	Remote Similarity	NPD1694	Approved
0.5918	Remote Similarity	NPD6116	Phase 1
0.5913	Remote Similarity	NPD5697	Approved
0.5909	Remote Similarity	NPD7902	Approved
0.5897	Remote Similarity	NPD6371	Approved
0.5897	Remote Similarity	NPD7102	Approved
0.5897	Remote Similarity	NPD7290	Approved
0.5897	Remote Similarity	NPD6883	Approved
0.5887	Remote Similarity	NPD6370	Approved
0.5877	Remote Similarity	NPD8170	Clinical (unspecified phase)
0.5868	Remote Similarity	NPD6009	Approved
0.5847	Remote Similarity	NPD6847	Approved
0.5847	Remote Similarity	NPD6617	Approved
0.5847	Remote Similarity	NPD6869	Approved
0.584	Remote Similarity	NPD7604	Phase 2
0.584	Remote Similarity	NPD8328	Phase 3
0.5833	Remote Similarity	NPD8171	Discontinued
0.5827	Remote Similarity	NPD8293	Discontinued
0.5826	Remote Similarity	NPD5739	Approved
0.5826	Remote Similarity	NPD7128	Approved
0.5826	Remote Similarity	NPD6402	Approved
0.5826	Remote Similarity	NPD6675	Approved
0.5816	Remote Similarity	NPD6117	Approved
0.5812	Remote Similarity	NPD6013	Approved
0.5812	Remote Similarity	NPD6012	Approved
0.5812	Remote Similarity	NPD6373	Approved
0.5812	Remote Similarity	NPD6014	Approved
0.5812	Remote Similarity	NPD6372	Approved
0.581	Remote Similarity	NPD7524	Approved
0.581	Remote Similarity	NPD4250	Approved
0.581	Remote Similarity	NPD4251	Approved
0.5806	Remote Similarity	NPD6015	Approved
0.5806	Remote Similarity	NPD5983	Phase 2
0.5806	Remote Similarity	NPD6016	Approved
0.5798	Remote Similarity	NPD6053	Discontinued
0.5794	Remote Similarity	NPD3168	Discontinued
0.5776	Remote Similarity	NPD6412	Phase 2
0.5769	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.576	Remote Similarity	NPD5988	Approved
0.5748	Remote Similarity	NPD6336	Discontinued
0.5741	Remote Similarity	NPD7637	Suspended
0.5738	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.5726	Remote Similarity	NPD6011	Approved
0.5726	Remote Similarity	NPD6059	Approved
0.5726	Remote Similarity	NPD7320	Approved
0.5714	Remote Similarity	NPD4249	Approved
0.5701	Remote Similarity	NPD1695	Approved
0.569	Remote Similarity	NPD6008	Approved
0.5688	Remote Similarity	NPD5778	Approved
0.5688	Remote Similarity	NPD6399	Phase 3
0.5688	Remote Similarity	NPD5779	Approved
0.5686	Remote Similarity	NPD1779	Approved
0.5686	Remote Similarity	NPD1780	Approved
0.5684	Remote Similarity	NPD4267	Clinical (unspecified phase)
0.5652	Remote Similarity	NPD7909	Approved
0.5641	Remote Similarity	NPD5701	Approved
0.5636	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.5636	Remote Similarity	NPD7900	Approved
0.5631	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.563	Remote Similarity	NPD4634	Approved
0.5619	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.5612	Remote Similarity	NPD1811	Approved
0.5612	Remote Similarity	NPD1810	Approved
0.5612	Remote Similarity	NPD6113	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