NPASS Compound

Structure

NPC49371 OpenBabel07101719252D 37 40 0 0 1 0 0 0 0 0999 V2000 2.9855 2.6396 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2424 3.3087 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9641 -3.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9641 -3.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4067 -1.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4067 0.9135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0032 1.9292 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3872 1.7953 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0563 2.5385 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5388 -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 -0.5909 2.0032 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 0.3090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3301 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0345 2.3305 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2601 1.2601 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1962 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5388 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9000 2.9543 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 5.1962 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3435 1.3795 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2111 0.9511 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 25 1 0 0 0 0 2 25 1 0 0 0 0 3 26 1 0 0 0 0 4 26 1 0 0 0 0 5 27 1 0 0 0 0 9 10 1 0 0 0 0 9 16 2 0 0 0 0 10 20 1 0 0 0 0 11 12 1 0 0 0 0 11 21 1 0 0 0 0 12 25 1 0 0 0 0 13 17 1 0 0 0 0 13 18 1 0 0 0 0 14 19 1 0 0 0 0 14 27 1 0 0 0 0 15 22 1 0 0 0 0 15 28 1 0 0 0 0 16 17 1 0 0 0 0 16 26 1 0 0 0 0 17 29 1 6 0 0 0 18 24 1 0 0 0 0 18 31 1 6 0 0 0 19 23 1 0 0 0 0 19 32 1 1 0 0 0 20 27 1 1 0 0 0 20 29 1 0 0 0 0 21 30 1 0 0 0 0 21 33 2 0 0 0 0 22 29 1 0 0 0 0 22 34 2 0 0 0 0 23 28 1 6 0 0 0 23 30 1 0 0 0 0 24 26 1 0 0 0 0 24 35 2 0 0 0 0 25 36 1 0 0 0 0 27 28 1 1 0 0 0 28 6 1 6 0 0 0 29 7 1 6 0 0 0 30 8 1 6 0 0 0 30 37 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	518.32
Volume:	544.196
LogP:	2.357
LogD:	1.514
LogS:	-4.237
# Rotatable Bonds:	5
TPSA:	132.13
# H-Bond Aceptor:	7
# H-Bond Donor:	4
# Rings:	4
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.411
Synthetic Accessibility Score:	5.369
Fsp3:	0.833
Lipinski Rule-of-5:	Accepted
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:	-5.006
MDCK Permeability:	1.157312908617314e-05
Pgp-inhibitor:	0.83
Pgp-substrate:	0.024
Human Intestinal Absorption (HIA):	0.043
20% Bioavailability (F20%):	0.946
30% Bioavailability (F30%):	0.874

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.866
Plasma Protein Binding (PPB):	64.24490356445312%
Volume Distribution (VD):	0.497
Pgp-substrate:	21.97529411315918%

ADMET: Metabolism

CYP1A2-inhibitor:	0.003
CYP1A2-substrate:	0.125
CYP2C19-inhibitor:	0.018
CYP2C19-substrate:	0.82
CYP2C9-inhibitor:	0.046
CYP2C9-substrate:	0.421
CYP2D6-inhibitor:	0.003
CYP2D6-substrate:	0.118
CYP3A4-inhibitor:	0.698
CYP3A4-substrate:	0.275

ADMET: Excretion

Clearance (CL):	4.417
Half-life (T1/2):	0.831

ADMET: Toxicity

hERG Blockers:	0.012
Human Hepatotoxicity (H-HT):	0.157
Drug-inuced Liver Injury (DILI):	0.272
AMES Toxicity:	0.042
Rat Oral Acute Toxicity:	0.954
Maximum Recommended Daily Dose:	0.898
Skin Sensitization:	0.131
Carcinogencity:	0.726
Eye Corrosion:	0.003
Eye Irritation:	0.016
Respiratory Toxicity:	0.215

Download Data

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

Natural Product: NPC49371

Natural Product ID:	NPC49371
*Common Name:**	Cucurbitacin R
IUPAC Name:	(2S,8S,9R,10R,13R,14S,16R,17R)-17-[(2R)-2,6-dihydroxy-6-methyl-3-oxoheptan-2-yl]-2,16-dihydroxy-4,4,9,13,14-pentamethyl-2,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthrene-3,11-dione
Synonyms:	Cucurbitacin R
Standard InCHIKey:	ITMUUFDDBRYVNJ-VOKXYEOFSA-N
Standard InCHI:	InChI=1S/C30H46O7/c1-25(2,36)12-11-21(33)30(8,37)23-19(32)14-27(5)20-10-9-16-17(13-18(31)24(35)26(16,3)4)29(20,7)22(34)15-28(23,27)6/h9,17-20,23,31-32,36-37H,10-15H2,1-8H3/t17-,18+,19-,20+,23+,27+,28-,29+,30+/m1/s1
SMILES:	CC(C)(CCC(=O)[C@@](C)([C@H]1[C@@H](C[C@@]2(C)[C@@H]3CC=C4[C@@H](C[C@@H](C(=O)C4(C)C)O)[C@]3(C)C(=O)C[C@]12C)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL564629
PubChem CID:	180535
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001686] Cucurbitacins

*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
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33269591]
NPO32650	conobea scoparioides	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7852999]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	1
Others	7

Activity Type	# Activity
Cell Line	4
Individual Protein	1
Others	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4306	Cell Line	JY	Homo sapiens	Inhibition	=	20.0	%	PMID[534545]
NPT4306	Cell Line	JY	Homo sapiens	Inhibition	=	22.0	%	PMID[534545]
NPT4306	Cell Line	JY	Homo sapiens	Inhibition	=	74.0	%	PMID[534545]
NPT4306	Cell Line	JY	Homo sapiens	Inhibition	=	7.0	%	PMID[534545]
NPT2536	Individual Protein	Leukocyte adhesion glycoprotein LFA-1 alpha	Homo sapiens	IC50	>	50000.0	nM	PMID[534545]
NPT2	Others	Unspecified		Inhibition	=	86.0	%	PMID[534545]
NPT2	Others	Unspecified		Inhibition	=	82.8	%	PMID[534545]
NPT2	Others	Unspecified		Inhibition	=	79.2	%	PMID[534545]

☑ 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 NPC49371 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	183
0.1-0.2	1312
0.2-0.3	5465
0.3-0.4	13451
0.4-0.5	8153
0.5-0.6	5820
0.6-0.7	5934
0.7-0.8	2104
0.8-0.85	170
0.85-0.9	91
0.9-0.95	12
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9368	High Similarity	NPC191892
0.9368	High Similarity	NPC117185
0.9255	High Similarity	NPC474720
0.9175	High Similarity	NPC196528
0.9082	High Similarity	NPC165873
0.9053	High Similarity	NPC15390
0.9043	High Similarity	NPC18509
0.8969	High Similarity	NPC311612
0.8901	High Similarity	NPC76879
0.8901	High Similarity	NPC326627
0.8901	High Similarity	NPC310010
0.8901	High Similarity	NPC477943
0.8876	High Similarity	NPC474218
0.8866	High Similarity	NPC87351
0.8854	High Similarity	NPC83709
0.8854	High Similarity	NPC144956
0.8842	High Similarity	NPC190554
0.8817	High Similarity	NPC233118
0.8804	High Similarity	NPC171441
0.8788	High Similarity	NPC257353
0.8764	High Similarity	NPC82902
0.875	High Similarity	NPC191565
0.8723	High Similarity	NPC111015
0.8723	High Similarity	NPC245972
0.8723	High Similarity	NPC196485
0.871	High Similarity	NPC185936
0.871	High Similarity	NPC168027
0.87	High Similarity	NPC43285
0.87	High Similarity	NPC83744
0.87	High Similarity	NPC58370
0.87	High Similarity	NPC477916
0.8696	High Similarity	NPC474245
0.8687	High Similarity	NPC137657
0.8687	High Similarity	NPC204833
0.8687	High Similarity	NPC209502
0.8681	High Similarity	NPC90652
0.8681	High Similarity	NPC317590
0.866	High Similarity	NPC218383
0.866	High Similarity	NPC154072
0.8641	High Similarity	NPC280782
0.8632	High Similarity	NPC472485
0.8617	High Similarity	NPC206810
0.8614	High Similarity	NPC329417
0.8602	High Similarity	NPC320026
0.8602	High Similarity	NPC46758
0.86	High Similarity	NPC296945
0.86	High Similarity	NPC85829
0.86	High Similarity	NPC202167
0.86	High Similarity	NPC319077
0.86	High Similarity	NPC150531
0.86	High Similarity	NPC49958
0.86	High Similarity	NPC302607
0.86	High Similarity	NPC149047
0.86	High Similarity	NPC152695
0.86	High Similarity	NPC476027
0.86	High Similarity	NPC97202
0.86	High Similarity	NPC214264
0.86	High Similarity	NPC260268
0.86	High Similarity	NPC48733
0.86	High Similarity	NPC50692
0.86	High Similarity	NPC171137
0.8587	High Similarity	NPC193360
0.8587	High Similarity	NPC471941
0.8587	High Similarity	NPC470417
0.8586	High Similarity	NPC140723
0.8586	High Similarity	NPC249187
0.8586	High Similarity	NPC247957
0.8586	High Similarity	NPC111323
0.8571	High Similarity	NPC51014
0.8571	High Similarity	NPC20688
0.8571	High Similarity	NPC327115
0.8571	High Similarity	NPC469994
0.8558	High Similarity	NPC73300
0.8558	High Similarity	NPC108721
0.8557	High Similarity	NPC477854
0.8542	High Similarity	NPC192428
0.8542	High Similarity	NPC477853
0.8542	High Similarity	NPC173272
0.8529	High Similarity	NPC214644
0.8529	High Similarity	NPC304495
0.8529	High Similarity	NPC470257
0.8515	High Similarity	NPC220229
0.8515	High Similarity	NPC185
0.8515	High Similarity	NPC475060
0.8511	High Similarity	NPC154101
0.85	High Similarity	NPC72255
0.85	High Similarity	NPC29705
0.8495	Intermediate Similarity	NPC186688
0.8495	Intermediate Similarity	NPC2983
0.8485	Intermediate Similarity	NPC477915
0.8447	Intermediate Similarity	NPC235077
0.8438	Intermediate Similarity	NPC48330
0.8438	Intermediate Similarity	NPC127063
0.8438	Intermediate Similarity	NPC272617
0.8438	Intermediate Similarity	NPC469599
0.8438	Intermediate Similarity	NPC472932
0.8438	Intermediate Similarity	NPC271195
0.8431	Intermediate Similarity	NPC94529
0.8431	Intermediate Similarity	NPC217201
0.8421	Intermediate Similarity	NPC470376
0.8421	Intermediate Similarity	NPC470375
0.8396	Intermediate Similarity	NPC148458
0.8387	Intermediate Similarity	NPC328539
0.8387	Intermediate Similarity	NPC328313
0.8384	Intermediate Similarity	NPC477052
0.8384	Intermediate Similarity	NPC477053
0.8384	Intermediate Similarity	NPC477051
0.8367	Intermediate Similarity	NPC147954
0.8352	Intermediate Similarity	NPC85774
0.8352	Intermediate Similarity	NPC59453
0.8352	Intermediate Similarity	NPC329043
0.8352	Intermediate Similarity	NPC58841
0.8352	Intermediate Similarity	NPC237712
0.8352	Intermediate Similarity	NPC161423
0.8352	Intermediate Similarity	NPC227064
0.8352	Intermediate Similarity	NPC144258
0.8352	Intermediate Similarity	NPC321187
0.8352	Intermediate Similarity	NPC214043
0.8352	Intermediate Similarity	NPC221758
0.835	Intermediate Similarity	NPC258543
0.835	Intermediate Similarity	NPC241927
0.835	Intermediate Similarity	NPC11710
0.8333	Intermediate Similarity	NPC209662
0.8333	Intermediate Similarity	NPC44063
0.8318	Intermediate Similarity	NPC239273
0.8317	Intermediate Similarity	NPC471293
0.83	Intermediate Similarity	NPC271980
0.83	Intermediate Similarity	NPC473928
0.83	Intermediate Similarity	NPC22388
0.83	Intermediate Similarity	NPC193934
0.83	Intermediate Similarity	NPC185530
0.83	Intermediate Similarity	NPC477054
0.8298	Intermediate Similarity	NPC275740
0.8298	Intermediate Similarity	NPC475921
0.8298	Intermediate Similarity	NPC54689
0.8298	Intermediate Similarity	NPC474704
0.8298	Intermediate Similarity	NPC32830
0.8298	Intermediate Similarity	NPC31985
0.8298	Intermediate Similarity	NPC1015
0.8298	Intermediate Similarity	NPC86319
0.8286	Intermediate Similarity	NPC100267
0.8286	Intermediate Similarity	NPC475524
0.8286	Intermediate Similarity	NPC71348
0.8286	Intermediate Similarity	NPC207251
0.8283	Intermediate Similarity	NPC110149
0.828	Intermediate Similarity	NPC472481
0.828	Intermediate Similarity	NPC472482
0.828	Intermediate Similarity	NPC472484
0.8269	Intermediate Similarity	NPC76084
0.8265	Intermediate Similarity	NPC57416
0.8265	Intermediate Similarity	NPC107243
0.8261	Intermediate Similarity	NPC471224
0.8261	Intermediate Similarity	NPC469948
0.8252	Intermediate Similarity	NPC65941
0.8247	Intermediate Similarity	NPC473170
0.8247	Intermediate Similarity	NPC472824
0.8242	Intermediate Similarity	NPC476082
0.8242	Intermediate Similarity	NPC278648
0.8235	Intermediate Similarity	NPC166607
0.8235	Intermediate Similarity	NPC231530
0.8235	Intermediate Similarity	NPC278628
0.8229	Intermediate Similarity	NPC472930
0.8229	Intermediate Similarity	NPC152897
0.8229	Intermediate Similarity	NPC474807
0.8229	Intermediate Similarity	NPC477855
0.8229	Intermediate Similarity	NPC243866
0.8229	Intermediate Similarity	NPC472942
0.8229	Intermediate Similarity	NPC66429
0.8218	Intermediate Similarity	NPC26478
0.8211	Intermediate Similarity	NPC100313
0.8211	Intermediate Similarity	NPC136801
0.8211	Intermediate Similarity	NPC289213
0.8208	Intermediate Similarity	NPC317210
0.8208	Intermediate Similarity	NPC202889
0.82	Intermediate Similarity	NPC474327
0.8191	Intermediate Similarity	NPC143767
0.8191	Intermediate Similarity	NPC131470
0.8191	Intermediate Similarity	NPC53911
0.8191	Intermediate Similarity	NPC44181
0.819	Intermediate Similarity	NPC118860
0.819	Intermediate Similarity	NPC214797
0.819	Intermediate Similarity	NPC43775
0.819	Intermediate Similarity	NPC231589
0.8182	Intermediate Similarity	NPC153792
0.8182	Intermediate Similarity	NPC114274
0.8182	Intermediate Similarity	NPC271387
0.8173	Intermediate Similarity	NPC2766
0.8172	Intermediate Similarity	NPC145879
0.8172	Intermediate Similarity	NPC474732
0.8172	Intermediate Similarity	NPC474733
0.8172	Intermediate Similarity	NPC474778
0.8172	Intermediate Similarity	NPC473168
0.8172	Intermediate Similarity	NPC31564
0.8163	Intermediate Similarity	NPC96859
0.8163	Intermediate Similarity	NPC328162
0.8163	Intermediate Similarity	NPC42042
0.8163	Intermediate Similarity	NPC249954
0.8163	Intermediate Similarity	NPC155676
0.8163	Intermediate Similarity	NPC305483
0.8152	Intermediate Similarity	NPC473246

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 NPC49371 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	156
0.1-0.2	1616
0.2-0.3	4217
0.3-0.4	2125
0.4-0.5	552
0.5-0.6	153
0.6-0.7	139
0.7-0.8	108
0.8-0.85	57
0.85-0.9	25
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9043	High Similarity	NPD4755	Approved
0.8901	High Similarity	NPD4753	Phase 2
0.8854	High Similarity	NPD5285	Approved
0.8854	High Similarity	NPD4700	Approved
0.8854	High Similarity	NPD4696	Approved
0.8854	High Similarity	NPD5286	Approved
0.8673	High Similarity	NPD5211	Phase 2
0.8673	High Similarity	NPD5225	Approved
0.8673	High Similarity	NPD4633	Approved
0.8673	High Similarity	NPD5224	Approved
0.8673	High Similarity	NPD5226	Approved
0.8632	High Similarity	NPD5210	Approved
0.8632	High Similarity	NPD4629	Approved
0.86	High Similarity	NPD5739	Approved
0.86	High Similarity	NPD6675	Approved
0.86	High Similarity	NPD6402	Approved
0.86	High Similarity	NPD7128	Approved
0.8586	High Similarity	NPD5175	Approved
0.8586	High Similarity	NPD5174	Approved
0.8571	High Similarity	NPD5223	Approved
0.8542	High Similarity	NPD4697	Phase 3
0.8529	High Similarity	NPD6373	Approved
0.8529	High Similarity	NPD6372	Approved
0.85	High Similarity	NPD5141	Approved
0.8495	Intermediate Similarity	NPD5328	Approved
0.8462	Intermediate Similarity	NPD5329	Approved
0.8454	Intermediate Similarity	NPD6084	Phase 2
0.8454	Intermediate Similarity	NPD6083	Phase 2
0.8447	Intermediate Similarity	NPD4634	Approved
0.8431	Intermediate Similarity	NPD6881	Approved
0.8431	Intermediate Similarity	NPD6899	Approved
0.8431	Intermediate Similarity	NPD7320	Approved
0.8416	Intermediate Similarity	NPD4767	Approved
0.8416	Intermediate Similarity	NPD4768	Approved
0.84	Intermediate Similarity	NPD4754	Approved
0.8365	Intermediate Similarity	NPD6650	Approved
0.8365	Intermediate Similarity	NPD6649	Approved
0.8352	Intermediate Similarity	NPD4786	Approved
0.8352	Intermediate Similarity	NPD3666	Approved
0.8352	Intermediate Similarity	NPD3133	Approved
0.8352	Intermediate Similarity	NPD3665	Phase 1
0.8352	Intermediate Similarity	NPD4197	Approved
0.8351	Intermediate Similarity	NPD5220	Clinical (unspecified phase)
0.8351	Intermediate Similarity	NPD5221	Approved
0.8351	Intermediate Similarity	NPD5222	Approved
0.8333	Intermediate Similarity	NPD5701	Approved
0.8333	Intermediate Similarity	NPD5697	Approved
0.8316	Intermediate Similarity	NPD6079	Approved
0.8269	Intermediate Similarity	NPD7290	Approved
0.8269	Intermediate Similarity	NPD7102	Approved
0.8269	Intermediate Similarity	NPD6883	Approved
0.8265	Intermediate Similarity	NPD5173	Approved
0.8252	Intermediate Similarity	NPD4729	Approved
0.8252	Intermediate Similarity	NPD5128	Approved
0.8252	Intermediate Similarity	NPD4730	Approved
0.8229	Intermediate Similarity	NPD4202	Approved
0.819	Intermediate Similarity	NPD6847	Approved
0.819	Intermediate Similarity	NPD6617	Approved
0.819	Intermediate Similarity	NPD8130	Phase 1
0.819	Intermediate Similarity	NPD6869	Approved
0.8182	Intermediate Similarity	NPD5696	Approved
0.8173	Intermediate Similarity	NPD6013	Approved
0.8173	Intermediate Similarity	NPD6012	Approved
0.8173	Intermediate Similarity	NPD6014	Approved
0.8172	Intermediate Similarity	NPD3618	Phase 1
0.8132	Intermediate Similarity	NPD3667	Approved
0.8132	Intermediate Similarity	NPD4221	Approved
0.8132	Intermediate Similarity	NPD4223	Phase 3
0.8113	Intermediate Similarity	NPD8297	Approved
0.8113	Intermediate Similarity	NPD6882	Approved
0.8095	Intermediate Similarity	NPD5247	Approved
0.8095	Intermediate Similarity	NPD5248	Approved
0.8095	Intermediate Similarity	NPD5251	Approved
0.8095	Intermediate Similarity	NPD5250	Approved
0.8095	Intermediate Similarity	NPD5249	Phase 3
0.8077	Intermediate Similarity	NPD6011	Approved
0.8061	Intermediate Similarity	NPD5695	Phase 3
0.8037	Intermediate Similarity	NPD4632	Approved
0.8019	Intermediate Similarity	NPD5216	Approved
0.8019	Intermediate Similarity	NPD5215	Approved
0.8019	Intermediate Similarity	NPD6401	Clinical (unspecified phase)
0.8019	Intermediate Similarity	NPD5217	Approved
0.7979	Intermediate Similarity	NPD5280	Approved
0.7979	Intermediate Similarity	NPD5690	Phase 2
0.7979	Intermediate Similarity	NPD5279	Phase 3
0.7979	Intermediate Similarity	NPD4694	Approved
0.7928	Intermediate Similarity	NPD6054	Approved
0.7928	Intermediate Similarity	NPD6059	Approved
0.7925	Intermediate Similarity	NPD5135	Approved
0.7925	Intermediate Similarity	NPD5134	Clinical (unspecified phase)
0.7925	Intermediate Similarity	NPD5169	Approved
0.7857	Intermediate Similarity	NPD6399	Phase 3
0.785	Intermediate Similarity	NPD5127	Approved
0.7849	Intermediate Similarity	NPD4788	Approved
0.7818	Intermediate Similarity	NPD6009	Approved
0.7789	Intermediate Similarity	NPD4688	Approved
0.7789	Intermediate Similarity	NPD4690	Approved
0.7789	Intermediate Similarity	NPD5205	Approved
0.7789	Intermediate Similarity	NPD3574	Clinical (unspecified phase)
0.7789	Intermediate Similarity	NPD4693	Phase 3
0.7789	Intermediate Similarity	NPD4138	Approved
0.7789	Intermediate Similarity	NPD4689	Approved
0.7789	Intermediate Similarity	NPD6098	Approved
0.7788	Intermediate Similarity	NPD6370	Approved
0.7768	Intermediate Similarity	NPD6319	Approved
0.7732	Intermediate Similarity	NPD6904	Approved
0.7732	Intermediate Similarity	NPD6673	Approved
0.7732	Intermediate Similarity	NPD6080	Approved
0.7727	Intermediate Similarity	NPD6274	Approved
0.7714	Intermediate Similarity	NPD6008	Approved
0.7699	Intermediate Similarity	NPD6015	Approved
0.7699	Intermediate Similarity	NPD6016	Approved
0.7679	Intermediate Similarity	NPD7101	Approved
0.7679	Intermediate Similarity	NPD7100	Approved
0.7652	Intermediate Similarity	NPD7492	Approved
0.7642	Intermediate Similarity	NPD6412	Phase 2
0.7636	Intermediate Similarity	NPD5167	Approved
0.7632	Intermediate Similarity	NPD5988	Approved
0.7629	Intermediate Similarity	NPD6672	Approved
0.7629	Intermediate Similarity	NPD5737	Approved
0.7604	Intermediate Similarity	NPD6409	Approved
0.7604	Intermediate Similarity	NPD5330	Approved
0.7604	Intermediate Similarity	NPD6684	Approved
0.7604	Intermediate Similarity	NPD7521	Approved
0.7604	Intermediate Similarity	NPD7334	Approved
0.7604	Intermediate Similarity	NPD7146	Approved
0.7589	Intermediate Similarity	NPD6335	Approved
0.7586	Intermediate Similarity	NPD6616	Approved
0.7579	Intermediate Similarity	NPD3668	Phase 3
0.7576	Intermediate Similarity	NPD5284	Approved
0.7576	Intermediate Similarity	NPD5281	Approved
0.757	Intermediate Similarity	NPD5168	Approved
0.7565	Intermediate Similarity	NPD7604	Phase 2
0.7544	Intermediate Similarity	NPD6908	Approved
0.7544	Intermediate Similarity	NPD5983	Phase 2
0.7544	Intermediate Similarity	NPD6909	Approved
0.7527	Intermediate Similarity	NPD7525	Registered
0.7525	Intermediate Similarity	NPD6356	Clinical (unspecified phase)
0.7521	Intermediate Similarity	NPD7078	Approved
0.7521	Intermediate Similarity	NPD8293	Discontinued
0.75	Intermediate Similarity	NPD6317	Approved
0.75	Intermediate Similarity	NPD3617	Approved
0.7473	Intermediate Similarity	NPD3701	Clinical (unspecified phase)
0.7458	Intermediate Similarity	NPD7736	Approved
0.7449	Intermediate Similarity	NPD6903	Approved
0.7449	Intermediate Similarity	NPD7513	Clinical (unspecified phase)
0.7447	Intermediate Similarity	NPD4692	Approved
0.7447	Intermediate Similarity	NPD4139	Approved
0.7436	Intermediate Similarity	NPD6336	Discontinued
0.7434	Intermediate Similarity	NPD6314	Approved
0.7434	Intermediate Similarity	NPD6313	Approved
0.7429	Intermediate Similarity	NPD5091	Approved
0.7419	Intermediate Similarity	NPD4195	Approved
0.7416	Intermediate Similarity	NPD4243	Approved
0.74	Intermediate Similarity	NPD7515	Phase 2
0.74	Intermediate Similarity	NPD6050	Approved
0.74	Intermediate Similarity	NPD5693	Phase 1
0.7391	Intermediate Similarity	NPD6291	Clinical (unspecified phase)
0.7368	Intermediate Similarity	NPD4522	Approved
0.7363	Intermediate Similarity	NPD6942	Approved
0.7363	Intermediate Similarity	NPD7339	Approved
0.7347	Intermediate Similarity	NPD4751	Clinical (unspecified phase)
0.734	Intermediate Similarity	NPD4695	Discontinued
0.7327	Intermediate Similarity	NPD5133	Approved
0.732	Intermediate Similarity	NPD7520	Clinical (unspecified phase)
0.7311	Intermediate Similarity	NPD6033	Approved
0.7308	Intermediate Similarity	NPD7638	Approved
0.73	Intermediate Similarity	NPD5692	Phase 3
0.7257	Intermediate Similarity	NPD6868	Approved
0.7253	Intermediate Similarity	NPD4785	Approved
0.7253	Intermediate Similarity	NPD4784	Approved
0.7238	Intermediate Similarity	NPD7640	Approved
0.7238	Intermediate Similarity	NPD7639	Approved
0.7228	Intermediate Similarity	NPD5694	Approved
0.7174	Intermediate Similarity	NPD3703	Phase 2
0.7158	Intermediate Similarity	NPD6931	Approved
0.7158	Intermediate Similarity	NPD5368	Approved
0.7158	Intermediate Similarity	NPD6930	Phase 2
0.7143	Intermediate Similarity	NPD6053	Discontinued
0.7129	Intermediate Similarity	NPD4096	Approved
0.7113	Intermediate Similarity	NPD6695	Phase 3
0.7111	Intermediate Similarity	NPD4789	Approved
0.7111	Intermediate Similarity	NPD4245	Approved
0.7111	Intermediate Similarity	NPD4244	Approved
0.71	Intermediate Similarity	NPD5208	Approved
0.7087	Intermediate Similarity	NPD7748	Approved
0.7087	Intermediate Similarity	NPD6001	Approved
0.7065	Intermediate Similarity	NPD6926	Approved
0.7065	Intermediate Similarity	NPD6924	Approved
0.7059	Intermediate Similarity	NPD8035	Phase 2
0.7059	Intermediate Similarity	NPD6411	Approved
0.7059	Intermediate Similarity	NPD8034	Phase 2
0.7053	Intermediate Similarity	NPD6929	Approved
0.7048	Intermediate Similarity	NPD7902	Approved
0.7043	Intermediate Similarity	NPD7115	Discovery
0.7041	Intermediate Similarity	NPD7338	Clinical (unspecified phase)
0.7033	Intermediate Similarity	NPD4808	Clinical (unspecified phase)
0.7033	Intermediate Similarity	NPD4809	Clinical (unspecified phase)
0.7021	Intermediate Similarity	NPD6932	Approved
0.701	Intermediate Similarity	NPD6435	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