NPASS Compound

Structure

CID318135 OpenBabel06191716142D 45 50 0 0 1 0 0 0 0 0999 V2000 6.4007 1.5358 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7800 3.6775 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5100 2.4496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8366 -1.4491 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6733 -0.9661 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1822 1.4484 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1822 0.4830 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8367 1.4485 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6734 1.9315 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8738 2.2162 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8361 -1.4491 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6722 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1863 3.2988 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5412 1.7329 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.9312 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8337 2.3167 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3470 2.8965 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -0.9661 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6722 -0.9660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6733 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.2265 3.1983 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3467 1.9315 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5100 0.4830 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8367 0.4830 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3068 2.9971 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7422 0.7885 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8361 0.4830 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6606 0.4904 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8617 -0.4540 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1443 -1.1003 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6595 3.9792 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2259 -0.8022 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5100 1.4485 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 7.5791 4.1803 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6227 2.0310 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9184 2.2295 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8358 1.4637 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3780 1.1368 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7801 -0.7521 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3454 -2.0447 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0523 4.8607 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5086 -1.4486 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6996 3.8786 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0249 0.1422 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 16 1 0 0 0 0 4 5 1 0 0 0 0 4 18 2 0 0 0 0 6 7 1 0 0 0 0 6 22 1 0 0 0 0 7 23 1 0 0 0 0 8 9 1 0 0 0 0 8 24 1 0 0 0 0 9 33 1 0 0 0 0 10 16 1 0 0 0 0 10 25 1 0 0 0 0 11 18 1 0 0 0 0 11 19 1 0 0 0 0 12 19 1 0 0 0 0 12 27 1 0 0 0 0 13 21 1 0 0 0 0 13 35 1 0 0 0 0 14 36 1 0 0 0 0 15 37 1 0 0 0 0 16 21 2 0 0 0 0 17 2 1 6 0 0 0 17 22 1 0 0 0 0 18 34 1 0 0 0 0 19 43 1 1 0 0 0 20 5 1 6 0 0 0 20 23 1 0 0 0 0 20 24 1 0 0 0 0 21 31 1 0 0 0 0 22 33 1 1 0 0 0 23 33 1 1 0 0 0 24 34 1 1 0 0 0 25 17 1 6 0 0 0 25 44 1 0 0 0 0 26 14 1 1 0 0 0 26 28 1 0 0 0 0 26 45 1 0 0 0 0 27 34 1 0 0 0 0 27 38 2 0 0 0 0 28 29 1 0 0 0 0 28 39 1 6 0 0 0 29 30 1 0 0 0 0 29 40 1 1 0 0 0 30 32 1 0 0 0 0 30 41 1 6 0 0 0 31 42 2 0 0 0 0 31 44 1 0 0 0 0 32 43 1 1 0 0 0 32 45 1 0 0 0 0 33 3 1 1 0 0 0 34 15 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	634.34
Volume:	631.428
LogP:	1.855
LogD:	2.261
LogS:	-3.411
# Rotatable Bonds:	7
TPSA:	183.21
# H-Bond Aceptor:	11
# H-Bond Donor:	6
# Rings:	6
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.175
Synthetic Accessibility Score:	5.626
Fsp3:	0.824
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
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:	-5.895
MDCK Permeability:	3.5155888326698914e-05
Pgp-inhibitor:	0.57
Pgp-substrate:	0.855
Human Intestinal Absorption (HIA):	0.942
20% Bioavailability (F20%):	0.073
30% Bioavailability (F30%):	0.853

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.102
Plasma Protein Binding (PPB):	70.0096664428711%
Volume Distribution (VD):	0.499
Pgp-substrate:	7.730370044708252%

ADMET: Metabolism

CYP1A2-inhibitor:	0.006
CYP1A2-substrate:	0.098
CYP2C19-inhibitor:	0.008
CYP2C19-substrate:	0.52
CYP2C9-inhibitor:	0.007
CYP2C9-substrate:	0.043
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.047
CYP3A4-inhibitor:	0.511
CYP3A4-substrate:	0.473

ADMET: Excretion

Clearance (CL):	1.908
Half-life (T1/2):	0.883

ADMET: Toxicity

hERG Blockers:	0.053
Human Hepatotoxicity (H-HT):	0.177
Drug-inuced Liver Injury (DILI):	0.064
AMES Toxicity:	0.308
Rat Oral Acute Toxicity:	0.197
Maximum Recommended Daily Dose:	0.543
Skin Sensitization:	0.165
Carcinogencity:	0.762
Eye Corrosion:	0.003
Eye Irritation:	0.012
Respiratory Toxicity:	0.894

Download Data

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

Natural Product: NPC318135

Natural Product ID:	NPC318135
*Common Name:**	Withalongolide I
IUPAC Name:	(2R)-5-(hydroxymethyl)-2-[(1S)-1-[(3R,8S,9S,10R,13S,14S,17R)-10-(hydroxymethyl)-13-methyl-1-oxo-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]ethyl]-4-methyl-2,3-dihydropyran-6-one
Synonyms:	withalongolide I
Standard InCHIKey:	PRNFAKRMKREHJM-XYLPFXPVSA-N
Standard InCHI:	InChI=1S/C34H50O11/c1-16-10-25(44-31(42)21(16)13-35)17(2)22-6-7-23-20-5-4-18-11-19(43-32-30(41)29(40)28(39)26(14-36)45-32)12-27(38)34(18,15-37)24(20)8-9-33(22,23)3/h4,17,19-20,22-26,28-30,32,35-37,39-41H,5-15H2,1-3H3/t17-,19+,20-,22+,23-,24-,25+,26+,28+,29-,30+,32+,33+,34-/m0/s1
SMILES:	CC1=C(C(=O)OC(C1)C(C)C2CCC3C2(CCC4C3CC=C5C4(C(=O)CC(C5)OC6C(C(C(C(O6)CO)O)O)O)CO)C)CO
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1934461
PubChem CID:	56926205
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 [CHEMONTID:0001561] Withanolide glycosides 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
NPO14874	Physalis longifolia	Species	Solanaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[22098611]
NPO14874	Physalis longifolia	Species	Solanaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[22098611]
NPO14874	Physalis longifolia	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	5

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

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT169	Cell Line	B16-F10	Mus musculus	IC50	>	10000.0	nM	PMID[520654]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	IC50	>	10000.0	nM	PMID[520654]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[520654]
NPT27	Others	Unspecified		IC50	>	10000.0	nM	PMID[520654]

☑ 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 NPC318135 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	260
0.1-0.2	1502
0.2-0.3	4231
0.3-0.4	7402
0.4-0.5	11569
0.5-0.6	8020
0.6-0.7	5803
0.7-0.8	3150
0.8-0.85	677
0.85-0.9	74
0.9-0.95	8
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9417	High Similarity	NPC173347
0.9412	High Similarity	NPC245094
0.9231	High Similarity	NPC129434
0.9224	High Similarity	NPC232258
0.918	High Similarity	NPC231240
0.9174	High Similarity	NPC476966
0.9106	High Similarity	NPC316915
0.9091	High Similarity	NPC311534
0.9068	High Similarity	NPC202051
0.8974	High Similarity	NPC291564
0.8966	High Similarity	NPC207637
0.8908	High Similarity	NPC170084
0.8908	High Similarity	NPC476204
0.8852	High Similarity	NPC42399
0.8772	High Similarity	NPC118225
0.8772	High Similarity	NPC246205
0.877	High Similarity	NPC47113
0.877	High Similarity	NPC174367
0.875	High Similarity	NPC475182
0.8739	High Similarity	NPC122971
0.872	High Similarity	NPC471855
0.8718	High Similarity	NPC473882
0.871	High Similarity	NPC473593
0.8699	High Similarity	NPC329784
0.8699	High Similarity	NPC240070
0.8699	High Similarity	NPC146456
0.8699	High Similarity	NPC117702
0.8699	High Similarity	NPC471357
0.8699	High Similarity	NPC469757
0.8689	High Similarity	NPC177820
0.8689	High Similarity	NPC30188
0.8684	High Similarity	NPC295389
0.8678	High Similarity	NPC269642
0.8678	High Similarity	NPC28532
0.8667	High Similarity	NPC476150
0.8667	High Similarity	NPC129393
0.8667	High Similarity	NPC476127
0.8667	High Similarity	NPC470312
0.8655	High Similarity	NPC473617
0.8655	High Similarity	NPC239293
0.8655	High Similarity	NPC473828
0.8651	High Similarity	NPC146857
0.8651	High Similarity	NPC32793
0.8651	High Similarity	NPC247190
0.8651	High Similarity	NPC116075
0.8651	High Similarity	NPC469749
0.8629	High Similarity	NPC473620
0.8607	High Similarity	NPC469789
0.8607	High Similarity	NPC27363
0.8583	High Similarity	NPC329636
0.8583	High Similarity	NPC477071
0.8583	High Similarity	NPC319570
0.8571	High Similarity	NPC473968
0.8571	High Similarity	NPC474483
0.856	High Similarity	NPC86159
0.856	High Similarity	NPC469751
0.856	High Similarity	NPC469755
0.856	High Similarity	NPC469753
0.856	High Similarity	NPC197707
0.856	High Similarity	NPC329986
0.856	High Similarity	NPC10823
0.856	High Similarity	NPC471361
0.856	High Similarity	NPC251866
0.856	High Similarity	NPC140092
0.856	High Similarity	NPC180079
0.856	High Similarity	NPC70542
0.856	High Similarity	NPC471359
0.856	High Similarity	NPC89514
0.856	High Similarity	NPC232785
0.856	High Similarity	NPC284406
0.856	High Similarity	NPC471407
0.856	High Similarity	NPC9499
0.856	High Similarity	NPC125077
0.856	High Similarity	NPC471352
0.856	High Similarity	NPC17896
0.856	High Similarity	NPC469754
0.856	High Similarity	NPC471360
0.856	High Similarity	NPC276838
0.856	High Similarity	NPC6108
0.856	High Similarity	NPC188234
0.856	High Similarity	NPC219085
0.856	High Similarity	NPC471358
0.856	High Similarity	NPC469752
0.8559	High Similarity	NPC165439
0.8559	High Similarity	NPC472274
0.8559	High Similarity	NPC74727
0.8559	High Similarity	NPC181145
0.8548	High Similarity	NPC298841
0.8547	High Similarity	NPC210420
0.8547	High Similarity	NPC474265
0.8537	High Similarity	NPC470922
0.8537	High Similarity	NPC3381
0.8537	High Similarity	NPC248202
0.8534	High Similarity	NPC154856
0.8534	High Similarity	NPC475317
0.8534	High Similarity	NPC52241
0.8534	High Similarity	NPC83005
0.8525	High Similarity	NPC470265
0.8525	High Similarity	NPC23786
0.8525	High Similarity	NPC156789
0.8516	High Similarity	NPC158350
0.8516	High Similarity	NPC194716
0.8512	High Similarity	NPC281840
0.8512	High Similarity	NPC48692
0.8509	High Similarity	NPC210178
0.85	High Similarity	NPC475632
0.85	High Similarity	NPC45475
0.85	High Similarity	NPC86020
0.8492	Intermediate Similarity	NPC476074
0.8492	Intermediate Similarity	NPC262796
0.8492	Intermediate Similarity	NPC213634
0.8492	Intermediate Similarity	NPC329993
0.8492	Intermediate Similarity	NPC475377
0.8492	Intermediate Similarity	NPC264566
0.8492	Intermediate Similarity	NPC172374
0.8492	Intermediate Similarity	NPC134914
0.8492	Intermediate Similarity	NPC45346
0.8492	Intermediate Similarity	NPC478064
0.8492	Intermediate Similarity	NPC173435
0.8492	Intermediate Similarity	NPC475167
0.8492	Intermediate Similarity	NPC301639
0.8492	Intermediate Similarity	NPC477197
0.8492	Intermediate Similarity	NPC478065
0.848	Intermediate Similarity	NPC477078
0.848	Intermediate Similarity	NPC475281
0.848	Intermediate Similarity	NPC477075
0.848	Intermediate Similarity	NPC329923
0.8475	Intermediate Similarity	NPC62696
0.8475	Intermediate Similarity	NPC75167
0.8475	Intermediate Similarity	NPC293038
0.8475	Intermediate Similarity	NPC311592
0.8475	Intermediate Similarity	NPC260665
0.8475	Intermediate Similarity	NPC251309
0.8468	Intermediate Similarity	NPC473635
0.8468	Intermediate Similarity	NPC250556
0.8468	Intermediate Similarity	NPC469750
0.8468	Intermediate Similarity	NPC293112
0.8462	Intermediate Similarity	NPC79250
0.8462	Intermediate Similarity	NPC285410
0.8462	Intermediate Similarity	NPC290746
0.8462	Intermediate Similarity	NPC263827
0.8462	Intermediate Similarity	NPC250481
0.8462	Intermediate Similarity	NPC75616
0.8455	Intermediate Similarity	NPC160084
0.845	Intermediate Similarity	NPC251998
0.845	Intermediate Similarity	NPC329675
0.845	Intermediate Similarity	NPC289700
0.845	Intermediate Similarity	NPC59288
0.845	Intermediate Similarity	NPC62172
0.8443	Intermediate Similarity	NPC46570
0.8443	Intermediate Similarity	NPC67569
0.843	Intermediate Similarity	NPC475775
0.843	Intermediate Similarity	NPC476529
0.843	Intermediate Similarity	NPC197003
0.843	Intermediate Similarity	NPC161738
0.843	Intermediate Similarity	NPC475834
0.843	Intermediate Similarity	NPC475041
0.843	Intermediate Similarity	NPC474179
0.843	Intermediate Similarity	NPC190939
0.8425	Intermediate Similarity	NPC478153
0.8425	Intermediate Similarity	NPC478152
0.8425	Intermediate Similarity	NPC155529
0.8425	Intermediate Similarity	NPC478150
0.8417	Intermediate Similarity	NPC477252
0.8417	Intermediate Similarity	NPC309433
0.8413	Intermediate Similarity	NPC477079
0.8413	Intermediate Similarity	NPC477076
0.8413	Intermediate Similarity	NPC470912
0.8413	Intermediate Similarity	NPC470913
0.8413	Intermediate Similarity	NPC477196
0.8413	Intermediate Similarity	NPC477077
0.8403	Intermediate Similarity	NPC474557
0.8403	Intermediate Similarity	NPC116024
0.8403	Intermediate Similarity	NPC102088
0.8403	Intermediate Similarity	NPC475163
0.8403	Intermediate Similarity	NPC220293
0.84	Intermediate Similarity	NPC179412
0.84	Intermediate Similarity	NPC470516
0.84	Intermediate Similarity	NPC471356
0.84	Intermediate Similarity	NPC470780
0.839	Intermediate Similarity	NPC233003
0.839	Intermediate Similarity	NPC471967
0.839	Intermediate Similarity	NPC477253
0.839	Intermediate Similarity	NPC130427
0.839	Intermediate Similarity	NPC174836
0.8387	Intermediate Similarity	NPC32868
0.8387	Intermediate Similarity	NPC130229
0.8387	Intermediate Similarity	NPC469842
0.8387	Intermediate Similarity	NPC241456
0.8387	Intermediate Similarity	NPC7850
0.8387	Intermediate Similarity	NPC473474
0.8387	Intermediate Similarity	NPC8369
0.8387	Intermediate Similarity	NPC469841
0.8387	Intermediate Similarity	NPC6615
0.8385	Intermediate Similarity	NPC596
0.8385	Intermediate Similarity	NPC140045
0.8385	Intermediate Similarity	NPC295885
0.8376	Intermediate Similarity	NPC476766
0.8376	Intermediate Similarity	NPC129340
0.8374	Intermediate Similarity	NPC107493

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 NPC318135 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	226
0.1-0.2	1674
0.2-0.3	3714
0.3-0.4	2281
0.4-0.5	680
0.5-0.6	299
0.6-0.7	203
0.7-0.8	66
0.8-0.85	7
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.856	High Similarity	NPD7319	Approved
0.8468	Intermediate Similarity	NPD7507	Approved
0.8362	Intermediate Similarity	NPD6686	Approved
0.8306	Intermediate Similarity	NPD8328	Phase 3
0.8276	Intermediate Similarity	NPD6412	Phase 2
0.8145	Intermediate Similarity	NPD8513	Phase 3
0.8145	Intermediate Similarity	NPD8033	Approved
0.8115	Intermediate Similarity	NPD7115	Discovery
0.8065	Intermediate Similarity	NPD8294	Approved
0.8065	Intermediate Similarity	NPD8377	Approved
0.8047	Intermediate Similarity	NPD7736	Approved
0.8017	Intermediate Similarity	NPD8133	Approved
0.8	Intermediate Similarity	NPD8515	Approved
0.8	Intermediate Similarity	NPD8296	Approved
0.8	Intermediate Similarity	NPD7503	Approved
0.8	Intermediate Similarity	NPD8378	Approved
0.8	Intermediate Similarity	NPD8335	Approved
0.8	Intermediate Similarity	NPD8380	Approved
0.8	Intermediate Similarity	NPD8379	Approved
0.8	Intermediate Similarity	NPD8516	Approved
0.8	Intermediate Similarity	NPD8517	Approved
0.7969	Intermediate Similarity	NPD8293	Discontinued
0.7967	Intermediate Similarity	NPD8295	Clinical (unspecified phase)
0.7903	Intermediate Similarity	NPD7328	Approved
0.7903	Intermediate Similarity	NPD7327	Approved
0.784	Intermediate Similarity	NPD7516	Approved
0.7833	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7795	Intermediate Similarity	NPD6370	Approved
0.7674	Intermediate Similarity	NPD7492	Approved
0.7638	Intermediate Similarity	NPD6059	Approved
0.7638	Intermediate Similarity	NPD6054	Approved
0.7638	Intermediate Similarity	NPD6319	Approved
0.7615	Intermediate Similarity	NPD6616	Approved
0.7557	Intermediate Similarity	NPD7078	Approved
0.75	Intermediate Similarity	NPD8297	Approved
0.75	Intermediate Similarity	NPD6882	Approved
0.7458	Intermediate Similarity	NPD7639	Approved
0.7458	Intermediate Similarity	NPD7640	Approved
0.7442	Intermediate Similarity	NPD6016	Approved
0.7442	Intermediate Similarity	NPD6015	Approved
0.7419	Intermediate Similarity	NPD8413	Clinical (unspecified phase)
0.7402	Intermediate Similarity	NPD6009	Approved
0.7385	Intermediate Similarity	NPD5988	Approved
0.7373	Intermediate Similarity	NPD7638	Approved
0.736	Intermediate Similarity	NPD6053	Discontinued
0.7302	Intermediate Similarity	NPD4632	Approved
0.7295	Intermediate Similarity	NPD5739	Approved
0.7295	Intermediate Similarity	NPD6675	Approved
0.7295	Intermediate Similarity	NPD6402	Approved
0.7295	Intermediate Similarity	NPD7128	Approved
0.7258	Intermediate Similarity	NPD6372	Approved
0.7258	Intermediate Similarity	NPD6373	Approved
0.7241	Intermediate Similarity	NPD6399	Phase 3
0.7227	Intermediate Similarity	NPD4225	Approved
0.7213	Intermediate Similarity	NPD8170	Clinical (unspecified phase)
0.7177	Intermediate Similarity	NPD7320	Approved
0.7177	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7177	Intermediate Similarity	NPD6881	Approved
0.7177	Intermediate Similarity	NPD6899	Approved
0.7164	Intermediate Similarity	NPD8074	Phase 3
0.7143	Intermediate Similarity	NPD6649	Approved
0.7143	Intermediate Similarity	NPD8130	Phase 1
0.7143	Intermediate Similarity	NPD6650	Approved
0.712	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7111	Intermediate Similarity	NPD6033	Approved
0.7097	Intermediate Similarity	NPD5697	Approved
0.7097	Intermediate Similarity	NPD5701	Approved
0.7069	Intermediate Similarity	NPD46	Approved
0.7069	Intermediate Similarity	NPD6698	Approved
0.7063	Intermediate Similarity	NPD6371	Approved
0.7063	Intermediate Similarity	NPD4634	Approved
0.7063	Intermediate Similarity	NPD7102	Approved
0.7063	Intermediate Similarity	NPD7290	Approved
0.7063	Intermediate Similarity	NPD6883	Approved
0.7034	Intermediate Similarity	NPD7748	Approved
0.7016	Intermediate Similarity	NPD6008	Approved
0.7009	Intermediate Similarity	NPD7983	Approved
0.7008	Intermediate Similarity	NPD6869	Approved
0.7008	Intermediate Similarity	NPD6847	Approved
0.7008	Intermediate Similarity	NPD6617	Approved
0.7	Intermediate Similarity	NPD6083	Phase 2
0.7	Intermediate Similarity	NPD7902	Approved
0.7	Intermediate Similarity	NPD6084	Phase 2
0.6984	Remote Similarity	NPD6013	Approved
0.6984	Remote Similarity	NPD6012	Approved
0.6984	Remote Similarity	NPD6014	Approved
0.6983	Remote Similarity	NPD5328	Approved
0.694	Remote Similarity	NPD7604	Phase 2
0.694	Remote Similarity	NPD6067	Discontinued
0.6929	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6917	Remote Similarity	NPD5983	Phase 2
0.6911	Remote Similarity	NPD7632	Discontinued
0.6911	Remote Similarity	NPD5211	Phase 2
0.6905	Remote Similarity	NPD6011	Approved
0.6875	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6864	Remote Similarity	NPD7515	Phase 2
0.6864	Remote Similarity	NPD6079	Approved
0.6864	Remote Similarity	NPD7637	Suspended
0.6861	Remote Similarity	NPD8336	Approved
0.6861	Remote Similarity	NPD8337	Approved
0.686	Remote Similarity	NPD4755	Approved
0.6842	Remote Similarity	NPD4786	Approved
0.6838	Remote Similarity	NPD6336	Discontinued
0.6835	Remote Similarity	NPD7260	Phase 2
0.6825	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6815	Remote Similarity	NPD7830	Approved
0.6815	Remote Similarity	NPD7829	Approved
0.6807	Remote Similarity	NPD5778	Approved
0.6807	Remote Similarity	NPD5779	Approved
0.6803	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.68	Remote Similarity	NPD5141	Approved
0.6752	Remote Similarity	NPD6672	Approved
0.6752	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6752	Remote Similarity	NPD5737	Approved
0.675	Remote Similarity	NPD7900	Approved
0.675	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6748	Remote Similarity	NPD5285	Approved
0.6748	Remote Similarity	NPD5286	Approved
0.6748	Remote Similarity	NPD4700	Approved
0.6748	Remote Similarity	NPD4696	Approved
0.6728	Remote Similarity	NPD7799	Discontinued
0.6724	Remote Similarity	NPD6684	Approved
0.6724	Remote Similarity	NPD7334	Approved
0.6724	Remote Similarity	NPD6409	Approved
0.6724	Remote Similarity	NPD7521	Approved
0.6724	Remote Similarity	NPD5330	Approved
0.6724	Remote Similarity	NPD7146	Approved
0.6723	Remote Similarity	NPD6411	Approved
0.6696	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.6694	Remote Similarity	NPD5695	Phase 3
0.6693	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD3667	Approved
0.6667	Remote Similarity	NPD6274	Approved
0.6667	Remote Similarity	NPD8444	Approved
0.6667	Remote Similarity	NPD5696	Approved
0.6667	Remote Similarity	NPD6921	Approved
0.6643	Remote Similarity	NPD6914	Discontinued
0.6643	Remote Similarity	NPD5956	Approved
0.6642	Remote Similarity	NPD7101	Approved
0.6642	Remote Similarity	NPD7100	Approved
0.664	Remote Similarity	NPD4633	Approved
0.664	Remote Similarity	NPD5226	Approved
0.664	Remote Similarity	NPD5225	Approved
0.664	Remote Similarity	NPD5224	Approved
0.6639	Remote Similarity	NPD5221	Approved
0.6639	Remote Similarity	NPD5785	Approved
0.6639	Remote Similarity	NPD5222	Approved
0.6639	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6639	Remote Similarity	NPD4697	Phase 3
0.6639	Remote Similarity	NPD7839	Suspended
0.6614	Remote Similarity	NPD4767	Approved
0.6614	Remote Similarity	NPD4768	Approved
0.661	Remote Similarity	NPD6903	Approved
0.6594	Remote Similarity	NPD8451	Approved
0.6587	Remote Similarity	NPD5174	Approved
0.6587	Remote Similarity	NPD5175	Approved
0.6585	Remote Similarity	NPD5173	Approved
0.6583	Remote Similarity	NPD8035	Phase 2
0.6583	Remote Similarity	NPD8034	Phase 2
0.6583	Remote Similarity	NPD5693	Phase 1
0.6581	Remote Similarity	NPD3618	Phase 1
0.6569	Remote Similarity	NPD7642	Approved
0.6567	Remote Similarity	NPD6335	Approved
0.656	Remote Similarity	NPD5223	Approved
0.6557	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6555	Remote Similarity	NPD4753	Phase 2
0.6555	Remote Similarity	NPD6101	Approved
0.6555	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD3665	Phase 1
0.6552	Remote Similarity	NPD3666	Approved
0.6552	Remote Similarity	NPD3133	Approved
0.6549	Remote Similarity	NPD6845	Suspended
0.6549	Remote Similarity	NPD8338	Approved
0.6547	Remote Similarity	NPD8448	Approved
0.6544	Remote Similarity	NPD6908	Approved
0.6544	Remote Similarity	NPD6909	Approved
0.6541	Remote Similarity	NPD6868	Approved
0.6533	Remote Similarity	NPD7625	Phase 1
0.6529	Remote Similarity	NPD4202	Approved
0.6525	Remote Similarity	NPD8390	Approved
0.6525	Remote Similarity	NPD8392	Approved
0.6525	Remote Similarity	NPD8391	Approved
0.6522	Remote Similarity	NPD8299	Approved
0.6522	Remote Similarity	NPD8341	Approved
0.6522	Remote Similarity	NPD8342	Approved
0.6522	Remote Similarity	NPD8340	Approved
0.6512	Remote Similarity	NPD4729	Approved
0.6512	Remote Similarity	NPD4730	Approved
0.65	Remote Similarity	NPD7838	Discovery
0.6496	Remote Similarity	NPD8080	Discontinued
0.6493	Remote Similarity	NPD6317	Approved
0.6483	Remote Similarity	NPD7966	Clinical (unspecified phase)
0.6457	Remote Similarity	NPD4754	Approved
0.6444	Remote Similarity	NPD6314	Approved
0.6444	Remote Similarity	NPD6313	Approved
0.6434	Remote Similarity	NPD8449	Approved
0.6429	Remote Similarity	NPD5344	Discontinued
0.6417	Remote Similarity	NPD6904	Approved
0.6417	Remote Similarity	NPD6080	Approved
0.6417	Remote Similarity	NPD6673	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