NPASS Compound

Structure

NPC91034 OpenBabel07101718252D 33 37 0 0 1 0 0 0 0 0999 V2000 2.0074 -2.2294 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6180 1.9021 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4207 -0.1113 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7405 -1.3023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6065 1.1977 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4726 0.6977 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6720 2.2804 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6666 2.1759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3386 -1.8023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4726 -2.3023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8745 -0.8023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0085 -0.3023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6473 -0.5352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0511 -2.6453 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3383 -1.4863 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2872 1.1590 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.7405 0.6977 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3601 -1.6942 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2653 1.3669 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.8745 1.1977 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.7405 -0.3023 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.4726 -0.3023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3386 -0.8023 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9781 0.2079 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6065 -1.8023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 -0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0085 0.6977 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.6065 -0.8023 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9271 -2.8532 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2046 -0.3023 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7405 -2.3023 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2872 -1.1590 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 15 1 0 0 0 0 5 6 1 0 0 0 0 6 22 2 0 0 0 0 7 8 1 0 0 0 0 7 19 1 0 0 0 0 8 20 1 0 0 0 0 9 10 2 0 0 0 0 9 23 1 0 0 0 0 10 25 1 0 0 0 0 11 12 1 0 0 0 0 11 21 1 0 0 0 0 12 27 1 0 0 0 0 13 15 1 0 0 0 0 13 24 1 0 0 0 0 14 18 1 0 0 0 0 14 29 1 0 0 0 0 15 18 2 0 0 0 0 16 2 1 1 0 0 0 16 19 1 0 0 0 0 17 5 1 6 0 0 0 17 20 1 0 0 0 0 17 21 1 0 0 0 0 18 26 1 0 0 0 0 19 27 1 1 0 0 0 20 27 1 1 0 0 0 21 28 1 1 0 0 0 22 23 1 0 0 0 0 22 28 1 0 0 0 0 23 30 1 1 0 0 0 24 16 1 1 0 0 0 24 33 1 0 0 0 0 25 28 1 0 0 0 0 25 31 2 0 0 0 0 26 32 2 0 0 0 0 26 33 1 0 0 0 0 27 3 1 1 0 0 0 28 4 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	454.27
Volume:	480.831
LogP:	3.619
LogD:	3.305
LogS:	-4.174
# Rotatable Bonds:	3
TPSA:	80.67
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	5
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.504
Synthetic Accessibility Score:	5.124
Fsp3:	0.75
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-4.78
MDCK Permeability:	2.144304380635731e-05
Pgp-inhibitor:	0.998
Pgp-substrate:	0.489
Human Intestinal Absorption (HIA):	0.011
20% Bioavailability (F20%):	0.008
30% Bioavailability (F30%):	0.017

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.647
Plasma Protein Binding (PPB):	89.42845916748047%
Volume Distribution (VD):	0.525
Pgp-substrate:	4.025839805603027%

ADMET: Metabolism

CYP1A2-inhibitor:	0.062
CYP1A2-substrate:	0.489
CYP2C19-inhibitor:	0.294
CYP2C19-substrate:	0.623
CYP2C9-inhibitor:	0.355
CYP2C9-substrate:	0.091
CYP2D6-inhibitor:	0.013
CYP2D6-substrate:	0.283
CYP3A4-inhibitor:	0.866
CYP3A4-substrate:	0.568

ADMET: Excretion

Clearance (CL):	17.098
Half-life (T1/2):	0.728

ADMET: Toxicity

hERG Blockers:	0.044
Human Hepatotoxicity (H-HT):	0.279
Drug-inuced Liver Injury (DILI):	0.38
AMES Toxicity:	0.041
Rat Oral Acute Toxicity:	0.46
Maximum Recommended Daily Dose:	0.369
Skin Sensitization:	0.382
Carcinogencity:	0.366
Eye Corrosion:	0.01
Eye Irritation:	0.027
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: NPC91034

Natural Product ID:	NPC91034
*Common Name:**	5,6-Deoxywithaferin A
IUPAC Name:	(2R)-2-[(1S)-1-[(4S,8S,9S,10R,13S,14S,17R)-4-hydroxy-10,13-dimethyl-1-oxo-4,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]ethyl]-5-(hydroxymethyl)-4-methyl-2,3-dihydropyran-6-one
Synonyms:
Standard InCHIKey:	SHDXNRZAYHPFMX-OBQFDWBNSA-N
Standard InCHI:	InChI=1S/C28H38O5/c1-15-13-24(33-26(32)18(15)14-29)16(2)19-7-8-20-17-5-6-22-23(30)9-10-25(31)28(22,4)21(17)11-12-27(19,20)3/h6,9-10,16-17,19-21,23-24,29-30H,5,7-8,11-14H2,1-4H3/t16-,17-,19+,20-,21-,23-,24+,27+,28+/m0/s1
SMILES:	OCC1=C(C)C[C@@H](OC1=O)[C@H]([C@H]1CC[C@@H]2[C@]1(C)CC[C@H]1[C@H]2CC=C2[C@]1(C)C(=O)C=C[C@@H]2O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL3234469
PubChem CID:	90670439
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides 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
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1016/0031-9422(75)85035-7]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	roots	n.a.	n.a.	PMID[17190461]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19056281]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24079846]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26169123]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30776236]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15698	Withania somnifera	Species	Solanaceae	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	6
Others	1

Activity Type	# Activity
Cell Line	2
Individual Protein	1
NON-MOLECULAR	2
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4377	Individual Protein	Heat shock 70 kDa protein 6	Homo sapiens	FC	=	0.0	n.a.	PMID[502711]
NPT90	Cell Line	DU-145	Homo sapiens	IC50	=	10600.0	nM	PMID[502712]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	22600.0	nM	PMID[502712]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	5090.0	nM	PMID[502711]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	11900.0	nM	PMID[502712]
NPT2	Others	Unspecified		IC50	=	1800.0	nM	PMID[502712]
NPT27	Others	Unspecified		IC50	>	25000.0	nM	PMID[502712]

☑ 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 NPC91034 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	189
0.1-0.2	1059
0.2-0.3	3756
0.3-0.4	8104
0.4-0.5	13230
0.5-0.6	7174
0.6-0.7	6338
0.7-0.8	2551
0.8-0.85	245
0.85-0.9	45
0.9-0.95	5
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9417	High Similarity	NPC474315
0.9327	High Similarity	NPC191620
0.932	High Similarity	NPC29133
0.9314	High Similarity	NPC220155
0.9238	High Similarity	NPC122056
0.9231	High Similarity	NPC470961
0.9151	High Similarity	NPC147912
0.9151	High Similarity	NPC67259
0.9135	High Similarity	NPC37116
0.8981	High Similarity	NPC167606
0.8981	High Similarity	NPC286528
0.8981	High Similarity	NPC20302
0.8981	High Similarity	NPC140055
0.8962	High Similarity	NPC236217
0.8899	High Similarity	NPC50774
0.8899	High Similarity	NPC709
0.8889	High Similarity	NPC64318
0.8818	High Similarity	NPC264954
0.8807	High Similarity	NPC183580
0.8807	High Similarity	NPC312824
0.8807	High Similarity	NPC243065
0.8807	High Similarity	NPC470492
0.8807	High Similarity	NPC470493
0.8796	High Similarity	NPC474181
0.8785	High Similarity	NPC69291
0.8774	High Similarity	NPC473627
0.8739	High Similarity	NPC474370
0.8727	High Similarity	NPC186525
0.8725	High Similarity	NPC469657
0.8725	High Similarity	NPC244456
0.8713	High Similarity	NPC98868
0.8661	High Similarity	NPC67569
0.8661	High Similarity	NPC46570
0.8627	High Similarity	NPC476299
0.8627	High Similarity	NPC474012
0.8611	High Similarity	NPC221144
0.8586	High Similarity	NPC115021
0.8584	High Similarity	NPC107493
0.8584	High Similarity	NPC23786
0.8584	High Similarity	NPC153700
0.8584	High Similarity	NPC470265
0.8584	High Similarity	NPC88326
0.8559	High Similarity	NPC475913
0.8558	High Similarity	NPC470954
0.8544	High Similarity	NPC476223
0.8544	High Similarity	NPC310981
0.8544	High Similarity	NPC476240
0.8544	High Similarity	NPC99411
0.8544	High Similarity	NPC224720
0.8544	High Similarity	NPC472924
0.8529	High Similarity	NPC235464
0.8529	High Similarity	NPC197386
0.8529	High Similarity	NPC166745
0.8529	High Similarity	NPC478056
0.8515	High Similarity	NPC328371
0.8515	High Similarity	NPC472941
0.8515	High Similarity	NPC456
0.8509	High Similarity	NPC469789
0.85	High Similarity	NPC53685
0.8491	Intermediate Similarity	NPC475294
0.8482	Intermediate Similarity	NPC475834
0.8482	Intermediate Similarity	NPC474179
0.8482	Intermediate Similarity	NPC473270
0.8482	Intermediate Similarity	NPC473274
0.8468	Intermediate Similarity	NPC239273
0.8468	Intermediate Similarity	NPC470959
0.8468	Intermediate Similarity	NPC476965
0.8462	Intermediate Similarity	NPC475320
0.8455	Intermediate Similarity	NPC470953
0.8447	Intermediate Similarity	NPC287833
0.8447	Intermediate Similarity	NPC476274
0.844	Intermediate Similarity	NPC100267
0.844	Intermediate Similarity	NPC475524
0.8435	Intermediate Similarity	NPC3381
0.8435	Intermediate Similarity	NPC8374
0.8435	Intermediate Similarity	NPC8369
0.8435	Intermediate Similarity	NPC470494
0.8431	Intermediate Similarity	NPC202705
0.8431	Intermediate Similarity	NPC53844
0.8431	Intermediate Similarity	NPC156546
0.8431	Intermediate Similarity	NPC253826
0.8416	Intermediate Similarity	NPC318282
0.8416	Intermediate Similarity	NPC173875
0.8416	Intermediate Similarity	NPC469995
0.8416	Intermediate Similarity	NPC33473
0.8416	Intermediate Similarity	NPC174948
0.8416	Intermediate Similarity	NPC171395
0.8407	Intermediate Similarity	NPC476962
0.8396	Intermediate Similarity	NPC189863
0.8396	Intermediate Similarity	NPC266570
0.8384	Intermediate Similarity	NPC477147
0.8384	Intermediate Similarity	NPC273199
0.8384	Intermediate Similarity	NPC477149
0.8381	Intermediate Similarity	NPC236390
0.8381	Intermediate Similarity	NPC476889
0.8378	Intermediate Similarity	NPC148458
0.8378	Intermediate Similarity	NPC270929
0.8365	Intermediate Similarity	NPC473514
0.8364	Intermediate Similarity	NPC472929
0.8362	Intermediate Similarity	NPC293112
0.835	Intermediate Similarity	NPC316598
0.8348	Intermediate Similarity	NPC11895
0.8333	Intermediate Similarity	NPC29152
0.8333	Intermediate Similarity	NPC228477
0.8333	Intermediate Similarity	NPC473256
0.8333	Intermediate Similarity	NPC137911
0.8333	Intermediate Similarity	NPC470878
0.8319	Intermediate Similarity	NPC476960
0.8318	Intermediate Similarity	NPC472925
0.8317	Intermediate Similarity	NPC184870
0.8304	Intermediate Similarity	NPC472934
0.83	Intermediate Similarity	NPC472814
0.83	Intermediate Similarity	NPC177037
0.8291	Intermediate Similarity	NPC156797
0.8286	Intermediate Similarity	NPC40918
0.8286	Intermediate Similarity	NPC136289
0.8286	Intermediate Similarity	NPC155332
0.8286	Intermediate Similarity	NPC114540
0.8286	Intermediate Similarity	NPC293753
0.8286	Intermediate Similarity	NPC32577
0.8286	Intermediate Similarity	NPC204450
0.8286	Intermediate Similarity	NPC476890
0.8286	Intermediate Similarity	NPC195290
0.8283	Intermediate Similarity	NPC177141
0.8283	Intermediate Similarity	NPC214387
0.8283	Intermediate Similarity	NPC5509
0.8276	Intermediate Similarity	NPC81736
0.8276	Intermediate Similarity	NPC172154
0.8269	Intermediate Similarity	NPC51370
0.8261	Intermediate Similarity	NPC170538
0.8252	Intermediate Similarity	NPC121339
0.8252	Intermediate Similarity	NPC107243
0.8252	Intermediate Similarity	NPC320306
0.8252	Intermediate Similarity	NPC475894
0.8252	Intermediate Similarity	NPC476253
0.8246	Intermediate Similarity	NPC476961
0.8246	Intermediate Similarity	NPC79579
0.8235	Intermediate Similarity	NPC281134
0.8235	Intermediate Similarity	NPC209355
0.8235	Intermediate Similarity	NPC293052
0.8235	Intermediate Similarity	NPC476174
0.8235	Intermediate Similarity	NPC472932
0.823	Intermediate Similarity	NPC329736
0.823	Intermediate Similarity	NPC153440
0.8224	Intermediate Similarity	NPC472935
0.8218	Intermediate Similarity	NPC472930
0.8218	Intermediate Similarity	NPC474736
0.8214	Intermediate Similarity	NPC176840
0.8214	Intermediate Similarity	NPC476963
0.8214	Intermediate Similarity	NPC190286
0.8208	Intermediate Similarity	NPC111323
0.8208	Intermediate Similarity	NPC95899
0.8208	Intermediate Similarity	NPC72151
0.8208	Intermediate Similarity	NPC112009
0.8208	Intermediate Similarity	NPC473283
0.8208	Intermediate Similarity	NPC329345
0.8208	Intermediate Similarity	NPC476237
0.8208	Intermediate Similarity	NPC475526
0.82	Intermediate Similarity	NPC51486
0.8198	Intermediate Similarity	NPC472926
0.8198	Intermediate Similarity	NPC25909
0.819	Intermediate Similarity	NPC474327
0.819	Intermediate Similarity	NPC81530
0.819	Intermediate Similarity	NPC204812
0.819	Intermediate Similarity	NPC115899
0.819	Intermediate Similarity	NPC282524
0.819	Intermediate Similarity	NPC476888
0.819	Intermediate Similarity	NPC93744
0.8182	Intermediate Similarity	NPC470960
0.8182	Intermediate Similarity	NPC472928
0.8182	Intermediate Similarity	NPC324683
0.8174	Intermediate Similarity	NPC470418
0.8173	Intermediate Similarity	NPC57079
0.8173	Intermediate Similarity	NPC108368
0.8173	Intermediate Similarity	NPC471717
0.8165	Intermediate Similarity	NPC475065
0.8158	Intermediate Similarity	NPC5292
0.8158	Intermediate Similarity	NPC472933
0.8158	Intermediate Similarity	NPC61520
0.8155	Intermediate Similarity	NPC3772
0.8155	Intermediate Similarity	NPC7124
0.8155	Intermediate Similarity	NPC242848
0.8155	Intermediate Similarity	NPC120708
0.8151	Intermediate Similarity	NPC473593
0.8148	Intermediate Similarity	NPC473284
0.8148	Intermediate Similarity	NPC329048
0.8148	Intermediate Similarity	NPC330011
0.8148	Intermediate Similarity	NPC476958
0.8142	Intermediate Similarity	NPC472927
0.8142	Intermediate Similarity	NPC476959
0.8137	Intermediate Similarity	NPC470697
0.8131	Intermediate Similarity	NPC294259
0.8125	Intermediate Similarity	NPC284915
0.812	Intermediate Similarity	NPC241456
0.812	Intermediate Similarity	NPC32868
0.8119	Intermediate Similarity	NPC204341
0.8113	Intermediate Similarity	NPC56498
0.8113	Intermediate Similarity	NPC308726
0.8113	Intermediate Similarity	NPC320447
0.8113	Intermediate Similarity	NPC119601

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 NPC91034 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	160
0.1-0.2	1298
0.2-0.3	3467
0.3-0.4	2710
0.4-0.5	929
0.5-0.6	270
0.6-0.7	203
0.7-0.8	111
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8981	High Similarity	NPD7115	Discovery
0.82	Intermediate Similarity	NPD5785	Approved
0.8039	Intermediate Similarity	NPD6399	Phase 3
0.7905	Intermediate Similarity	NPD6084	Phase 2
0.7905	Intermediate Similarity	NPD6083	Phase 2
0.7885	Intermediate Similarity	NPD5695	Phase 3
0.783	Intermediate Similarity	NPD4225	Approved
0.7757	Intermediate Similarity	NPD7640	Approved
0.7757	Intermediate Similarity	NPD7639	Approved
0.7748	Intermediate Similarity	NPD6881	Approved
0.7748	Intermediate Similarity	NPD6899	Approved
0.77	Intermediate Similarity	NPD5363	Approved
0.7699	Intermediate Similarity	NPD6649	Approved
0.7699	Intermediate Similarity	NPD6650	Approved
0.7664	Intermediate Similarity	NPD5696	Approved
0.7664	Intermediate Similarity	NPD7638	Approved
0.7658	Intermediate Similarity	NPD5697	Approved
0.7647	Intermediate Similarity	NPD6672	Approved
0.7647	Intermediate Similarity	NPD5737	Approved
0.7647	Intermediate Similarity	NPD7513	Clinical (unspecified phase)
0.7624	Intermediate Similarity	NPD7334	Approved
0.7624	Intermediate Similarity	NPD7521	Approved
0.7624	Intermediate Similarity	NPD5330	Approved
0.7624	Intermediate Similarity	NPD7146	Approved
0.7624	Intermediate Similarity	NPD6409	Approved
0.7624	Intermediate Similarity	NPD6684	Approved
0.7611	Intermediate Similarity	NPD6883	Approved
0.7611	Intermediate Similarity	NPD7290	Approved
0.7611	Intermediate Similarity	NPD7102	Approved
0.76	Intermediate Similarity	NPD4786	Approved
0.7596	Intermediate Similarity	NPD6079	Approved
0.7596	Intermediate Similarity	NPD5284	Approved
0.7596	Intermediate Similarity	NPD5281	Approved
0.7596	Intermediate Similarity	NPD7637	Suspended
0.7596	Intermediate Similarity	NPD6411	Approved
0.7568	Intermediate Similarity	NPD6402	Approved
0.7568	Intermediate Similarity	NPD5739	Approved
0.7568	Intermediate Similarity	NPD7128	Approved
0.7568	Intermediate Similarity	NPD6675	Approved
0.7547	Intermediate Similarity	NPD4629	Approved
0.7547	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.7547	Intermediate Similarity	NPD5210	Approved
0.7544	Intermediate Similarity	NPD6617	Approved
0.7544	Intermediate Similarity	NPD6869	Approved
0.7544	Intermediate Similarity	NPD6847	Approved
0.7544	Intermediate Similarity	NPD8130	Phase 1
0.7525	Intermediate Similarity	NPD1694	Approved
0.7524	Intermediate Similarity	NPD5779	Approved
0.7524	Intermediate Similarity	NPD5778	Approved
0.7522	Intermediate Similarity	NPD6372	Approved
0.7522	Intermediate Similarity	NPD6373	Approved
0.7522	Intermediate Similarity	NPD6013	Approved
0.7522	Intermediate Similarity	NPD6014	Approved
0.7522	Intermediate Similarity	NPD6012	Approved
0.7478	Intermediate Similarity	NPD6882	Approved
0.7478	Intermediate Similarity	NPD6053	Discontinued
0.7478	Intermediate Similarity	NPD8297	Approved
0.7476	Intermediate Similarity	NPD6903	Approved
0.7455	Intermediate Similarity	NPD5211	Phase 2
0.7453	Intermediate Similarity	NPD7748	Approved
0.7451	Intermediate Similarity	NPD3618	Phase 1
0.7451	Intermediate Similarity	NPD5279	Phase 3
0.7434	Intermediate Similarity	NPD6011	Approved
0.7434	Intermediate Similarity	NPD7320	Approved
0.7429	Intermediate Similarity	NPD5693	Phase 1
0.7429	Intermediate Similarity	NPD7515	Phase 2
0.7426	Intermediate Similarity	NPD3666	Approved
0.7426	Intermediate Similarity	NPD3133	Approved
0.7426	Intermediate Similarity	NPD3665	Phase 1
0.7407	Intermediate Similarity	NPD7902	Approved
0.7404	Intermediate Similarity	NPD5328	Approved
0.7404	Intermediate Similarity	NPD4753	Phase 2
0.7404	Intermediate Similarity	NPD6101	Approved
0.7404	Intermediate Similarity	NPD5764	Clinical (unspecified phase)
0.74	Intermediate Similarity	NPD4752	Clinical (unspecified phase)
0.74	Intermediate Similarity	NPD4269	Approved
0.74	Intermediate Similarity	NPD4270	Approved
0.74	Intermediate Similarity	NPD3667	Approved
0.7347	Intermediate Similarity	NPD5784	Clinical (unspecified phase)
0.7345	Intermediate Similarity	NPD5701	Approved
0.7333	Intermediate Similarity	NPD5207	Approved
0.7321	Intermediate Similarity	NPD5141	Approved
0.7315	Intermediate Similarity	NPD5220	Clinical (unspecified phase)
0.7315	Intermediate Similarity	NPD5221	Approved
0.7315	Intermediate Similarity	NPD5222	Approved
0.7304	Intermediate Similarity	NPD6371	Approved
0.7282	Intermediate Similarity	NPD5786	Approved
0.7282	Intermediate Similarity	NPD3574	Clinical (unspecified phase)
0.7282	Intermediate Similarity	NPD5690	Phase 2
0.7281	Intermediate Similarity	NPD6686	Approved
0.7273	Intermediate Similarity	NPD5286	Approved
0.7273	Intermediate Similarity	NPD5285	Approved
0.7273	Intermediate Similarity	NPD4696	Approved
0.7264	Intermediate Similarity	NPD5694	Approved
0.7264	Intermediate Similarity	NPD6050	Approved
0.7248	Intermediate Similarity	NPD5173	Approved
0.7238	Intermediate Similarity	NPD6673	Approved
0.7238	Intermediate Similarity	NPD6080	Approved
0.7238	Intermediate Similarity	NPD6904	Approved
0.7222	Intermediate Similarity	NPD6356	Clinical (unspecified phase)
0.72	Intermediate Similarity	NPD4252	Approved
0.7193	Intermediate Similarity	NPD6412	Phase 2
0.719	Intermediate Similarity	NPD6319	Approved
0.717	Intermediate Similarity	NPD5692	Phase 3
0.7157	Intermediate Similarity	NPD5362	Discontinued
0.7156	Intermediate Similarity	NPD4697	Phase 3
0.7143	Intermediate Similarity	NPD5224	Approved
0.7143	Intermediate Similarity	NPD7632	Discontinued
0.7143	Intermediate Similarity	NPD5225	Approved
0.7143	Intermediate Similarity	NPD5226	Approved
0.7143	Intermediate Similarity	NPD4633	Approved
0.7143	Intermediate Similarity	NPD6868	Approved
0.713	Intermediate Similarity	NPD7901	Clinical (unspecified phase)
0.713	Intermediate Similarity	NPD7900	Approved
0.7129	Intermediate Similarity	NPD5369	Approved
0.7117	Intermediate Similarity	NPD6404	Discontinued
0.7107	Intermediate Similarity	NPD7100	Approved
0.7107	Intermediate Similarity	NPD7101	Approved
0.7103	Intermediate Similarity	NPD8034	Phase 2
0.7103	Intermediate Similarity	NPD8035	Phase 2
0.7097	Intermediate Similarity	NPD7492	Approved
0.7094	Intermediate Similarity	NPD6401	Clinical (unspecified phase)
0.7091	Intermediate Similarity	NPD4755	Approved
0.7087	Intermediate Similarity	NPD6400	Clinical (unspecified phase)
0.708	Intermediate Similarity	NPD5174	Approved
0.708	Intermediate Similarity	NPD5175	Approved
0.7075	Intermediate Similarity	NPD6051	Approved
0.7075	Intermediate Similarity	NPD7285	Clinical (unspecified phase)
0.7063	Intermediate Similarity	NPD7736	Approved
0.7059	Intermediate Similarity	NPD4221	Approved
0.7059	Intermediate Similarity	NPD4223	Phase 3
0.7054	Intermediate Similarity	NPD5223	Approved
0.7049	Intermediate Similarity	NPD6054	Approved
0.704	Intermediate Similarity	NPD6616	Approved
0.7037	Intermediate Similarity	NPD4202	Approved
0.7025	Intermediate Similarity	NPD6335	Approved
0.7019	Intermediate Similarity	NPD7520	Clinical (unspecified phase)
0.7019	Intermediate Similarity	NPD5329	Approved
0.7009	Intermediate Similarity	NPD4634	Approved
0.7008	Intermediate Similarity	NPD7319	Approved
0.7	Intermediate Similarity	NPD6274	Approved
0.6992	Remote Similarity	NPD7503	Approved
0.699	Remote Similarity	NPD7154	Phase 3
0.6984	Remote Similarity	NPD7078	Approved
0.6981	Remote Similarity	NPD5208	Approved
0.6975	Remote Similarity	NPD4632	Approved
0.6964	Remote Similarity	NPD4700	Approved
0.6957	Remote Similarity	NPD6008	Approved
0.6952	Remote Similarity	NPD6098	Approved
0.6952	Remote Similarity	NPD4623	Approved
0.6952	Remote Similarity	NPD5280	Approved
0.6952	Remote Similarity	NPD4519	Discontinued
0.6952	Remote Similarity	NPD4694	Approved
0.6942	Remote Similarity	NPD6317	Approved
0.6935	Remote Similarity	NPD6370	Approved
0.6923	Remote Similarity	NPD4197	Approved
0.6923	Remote Similarity	NPD3668	Phase 3
0.6905	Remote Similarity	NPD7507	Approved
0.6899	Remote Similarity	NPD7260	Phase 2
0.6887	Remote Similarity	NPD3573	Approved
0.6885	Remote Similarity	NPD6313	Approved
0.6885	Remote Similarity	NPD6314	Approved
0.6863	Remote Similarity	NPD4695	Discontinued
0.6863	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.6855	Remote Similarity	NPD6016	Approved
0.6855	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6855	Remote Similarity	NPD6015	Approved
0.6838	Remote Similarity	NPD4729	Approved
0.6838	Remote Similarity	NPD4730	Approved
0.6827	Remote Similarity	NPD4788	Approved
0.6818	Remote Similarity	NPD6001	Approved
0.6803	Remote Similarity	NPD6009	Approved
0.68	Remote Similarity	NPD5988	Approved
0.6792	Remote Similarity	NPD4138	Approved
0.6792	Remote Similarity	NPD4689	Approved
0.6792	Remote Similarity	NPD5205	Approved
0.6792	Remote Similarity	NPD4688	Approved
0.6792	Remote Similarity	NPD4690	Approved
0.6792	Remote Similarity	NPD4693	Phase 3
0.678	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6774	Remote Similarity	NPD6059	Approved
0.6765	Remote Similarity	NPD4195	Approved
0.6757	Remote Similarity	NPD5654	Approved
0.6752	Remote Similarity	NPD6614	Approved
0.6752	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6746	Remote Similarity	NPD7604	Phase 2
0.6731	Remote Similarity	NPD6435	Approved
0.6731	Remote Similarity	NPD5209	Approved
0.6723	Remote Similarity	NPD5249	Phase 3
0.6723	Remote Similarity	NPD5251	Approved
0.6723	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6723	Remote Similarity	NPD5247	Approved
0.6723	Remote Similarity	NPD5250	Approved
0.6723	Remote Similarity	NPD5248	Approved
0.672	Remote Similarity	NPD6909	Approved
0.672	Remote Similarity	NPD5983	Phase 2
0.672	Remote Similarity	NPD8513	Phase 3
0.672	Remote Similarity	NPD6908	Approved
0.6719	Remote Similarity	NPD8293	Discontinued
0.67	Remote Similarity	NPD6942	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