NPASS Compound

Structure

CID196931 OpenBabel06191715582D 29 33 0 0 1 0 0 0 0 0999 V2000 -1.7197 0.9929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5344 0.4878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6896 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0005 1.9507 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6885 -0.9748 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8442 1.4629 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8442 -1.4622 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0206 1.3304 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3789 1.9505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6893 2.9260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1850 -0.2377 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8452 2.4385 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5331 0.4867 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5344 1.4633 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6891 -0.0003 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8448 1.4633 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8448 0.4878 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3786 2.9255 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5338 3.4133 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9737 1.1275 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8443 0.4874 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6896 1.9510 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 1.0480 3.3922 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2445 3.4258 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5340 4.4133 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6981 1.7794 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0753 0.1584 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 21 1 0 0 0 0 2 3 1 0 0 0 0 2 14 1 0 0 0 0 3 17 1 0 0 0 0 4 6 1 0 0 0 0 4 16 1 0 0 0 0 5 7 1 0 0 0 0 5 15 1 0 0 0 0 6 21 1 0 0 0 0 7 23 1 0 0 0 0 8 13 2 0 0 0 0 8 20 1 0 0 0 0 9 14 1 0 0 0 0 9 18 1 0 0 0 0 10 19 1 0 0 0 0 10 22 1 0 0 0 0 11 13 1 0 0 0 0 11 29 1 0 0 0 0 12 24 2 0 0 0 0 13 15 1 0 0 0 0 14 22 1 6 0 0 0 15 21 1 6 0 0 0 16 17 1 0 0 0 0 16 22 1 6 0 0 0 17 23 1 1 0 0 0 18 19 1 0 0 0 0 18 25 1 6 0 0 0 19 26 1 1 0 0 0 20 27 2 0 0 0 0 20 29 1 0 0 0 0 21 23 1 6 0 0 0 22 12 1 6 0 0 0 23 28 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	404.22
Volume:	408.414
LogP:	1.682
LogD:	1.117
LogS:	-3.068
# Rotatable Bonds:	2
TPSA:	111.13
# H-Bond Aceptor:	6
# H-Bond Donor:	4
# Rings:	5
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.564
Synthetic Accessibility Score:	5.088
Fsp3:	0.783
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.515
MDCK Permeability:	1.0734463103290182e-05
Pgp-inhibitor:	0.025
Pgp-substrate:	0.995
Human Intestinal Absorption (HIA):	0.465
20% Bioavailability (F20%):	0.996
30% Bioavailability (F30%):	0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.642
Plasma Protein Binding (PPB):	64.99925994873047%
Volume Distribution (VD):	0.854
Pgp-substrate:	24.590843200683594%

ADMET: Metabolism

CYP1A2-inhibitor:	0.014
CYP1A2-substrate:	0.196
CYP2C19-inhibitor:	0.007
CYP2C19-substrate:	0.203
CYP2C9-inhibitor:	0.01
CYP2C9-substrate:	0.434
CYP2D6-inhibitor:	0.01
CYP2D6-substrate:	0.149
CYP3A4-inhibitor:	0.681
CYP3A4-substrate:	0.136

ADMET: Excretion

Clearance (CL):	7.332
Half-life (T1/2):	0.427

ADMET: Toxicity

hERG Blockers:	0.17
Human Hepatotoxicity (H-HT):	0.289
Drug-inuced Liver Injury (DILI):	0.08
AMES Toxicity:	0.022
Rat Oral Acute Toxicity:	0.809
Maximum Recommended Daily Dose:	0.93
Skin Sensitization:	0.843
Carcinogencity:	0.675
Eye Corrosion:	0.009
Eye Irritation:	0.039
Respiratory Toxicity:	0.962

Download Data

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

Natural Product: NPC196931

Natural Product ID:	NPC196931
*Common Name:**	Calotropagenin
IUPAC Name:	(2R,3R,5S,8R,9S,10R,13R,14S,17R)-2,3,14-trihydroxy-13-methyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-10-carbaldehyde
Synonyms:	Calotropagenin
Standard InCHIKey:	VRDLGTLMAZPOMK-CSWSNCTRSA-N
Standard InCHI:	InChI=1S/C23H32O6/c1-21-6-4-16-17(3-2-14-9-18(25)19(26)10-22(14,16)12-24)23(21,28)7-5-15(21)13-8-20(27)29-11-13/h8,12,14-19,25-26,28H,2-7,9-11H2,1H3/t14-,15+,16-,17+,18+,19+,21+,22+,23-/m0/s1
SMILES:	O=C[C@]12C[C@@H](O)[C@@H](C[C@@H]1CC[C@@H]1[C@@H]2CC[C@]2([C@]1(O)CC[C@@H]2C1=CC(=O)OC1)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL495033
PubChem CID:	14134976
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides 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
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16252914]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19251412]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3369	Anemone narcissiflora	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2175	Hyperbaena columbica	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8349	Uga sinensis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO26375	Viburnum grandifolium	Species	Adoxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9165	Asclepias curassavica	Species	Apocynaceae	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	3

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT65	Cell Line	HepG2	Homo sapiens	IC50	=	56610.0	nM	PMID[569153]
NPT80	Cell Line	Raji	Homo sapiens	IC50	=	24280.0	nM	PMID[569153]
NPT90	Cell Line	DU-145	Homo sapiens	IC50	=	480.0	nM	PMID[569154]

☑ 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 NPC196931 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	234
0.1-0.2	1396
0.2-0.3	4257
0.3-0.4	8317
0.4-0.5	12804
0.5-0.6	5788
0.6-0.7	6588
0.7-0.8	2929
0.8-0.85	288
0.85-0.9	90
0.9-0.95	4
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9273	High Similarity	NPC72772
0.9273	High Similarity	NPC469794
0.8972	High Similarity	NPC186668
0.8929	High Similarity	NPC49492
0.8929	High Similarity	NPC266728
0.8919	High Similarity	NPC962
0.8908	High Similarity	NPC253456
0.8908	High Similarity	NPC16569
0.8908	High Similarity	NPC159338
0.8889	High Similarity	NPC250556
0.8889	High Similarity	NPC469750
0.886	High Similarity	NPC475041
0.8833	High Similarity	NPC93416
0.8833	High Similarity	NPC42670
0.8833	High Similarity	NPC19124
0.8824	High Similarity	NPC91
0.8814	High Similarity	NPC179412
0.8814	High Similarity	NPC471356
0.8785	High Similarity	NPC472821
0.8774	High Similarity	NPC222875
0.8774	High Similarity	NPC25177
0.8774	High Similarity	NPC295110
0.8774	High Similarity	NPC247701
0.8774	High Similarity	NPC268829
0.876	High Similarity	NPC225385
0.876	High Similarity	NPC298783
0.876	High Similarity	NPC157817
0.876	High Similarity	NPC104585
0.876	High Similarity	NPC477709
0.876	High Similarity	NPC88668
0.876	High Similarity	NPC476221
0.875	High Similarity	NPC250109
0.8718	High Similarity	NPC27363
0.8673	High Similarity	NPC178289
0.8667	High Similarity	NPC471361
0.8667	High Similarity	NPC469752
0.8667	High Similarity	NPC17896
0.8667	High Similarity	NPC70542
0.8667	High Similarity	NPC284406
0.8667	High Similarity	NPC6108
0.8667	High Similarity	NPC231529
0.8667	High Similarity	NPC9499
0.8667	High Similarity	NPC232785
0.8667	High Similarity	NPC86159
0.8667	High Similarity	NPC188234
0.8667	High Similarity	NPC469755
0.8667	High Similarity	NPC10823
0.8667	High Similarity	NPC276838
0.8667	High Similarity	NPC471358
0.8667	High Similarity	NPC471359
0.8667	High Similarity	NPC197707
0.8667	High Similarity	NPC471360
0.8667	High Similarity	NPC125077
0.8667	High Similarity	NPC89514
0.8667	High Similarity	NPC251866
0.8667	High Similarity	NPC180079
0.8667	High Similarity	NPC469753
0.8667	High Similarity	NPC469751
0.8667	High Similarity	NPC219085
0.8667	High Similarity	NPC469754
0.8667	High Similarity	NPC471352
0.8667	High Similarity	NPC140092
0.8667	High Similarity	NPC329986
0.8661	High Similarity	NPC470063
0.8649	High Similarity	NPC76084
0.8632	High Similarity	NPC269642
0.8621	High Similarity	NPC109973
0.8611	High Similarity	NPC112009
0.8611	High Similarity	NPC97487
0.8611	High Similarity	NPC196471
0.8611	High Similarity	NPC189588
0.8611	High Similarity	NPC10232
0.8611	High Similarity	NPC160583
0.8611	High Similarity	NPC187302
0.8607	High Similarity	NPC142756
0.8598	High Similarity	NPC471412
0.8596	High Similarity	NPC138372
0.8596	High Similarity	NPC106228
0.8559	High Similarity	NPC473979
0.8532	High Similarity	NPC209502
0.8532	High Similarity	NPC204833
0.8522	High Similarity	NPC284068
0.8509	High Similarity	NPC326542
0.8505	High Similarity	NPC471413
0.8505	High Similarity	NPC201406
0.8505	High Similarity	NPC251680
0.85	High Similarity	NPC471357
0.85	High Similarity	NPC469757
0.85	High Similarity	NPC329784
0.85	High Similarity	NPC240070
0.85	High Similarity	NPC117702
0.85	High Similarity	NPC146456
0.8496	Intermediate Similarity	NPC207251
0.8491	Intermediate Similarity	NPC231751
0.8482	Intermediate Similarity	NPC179642
0.8475	Intermediate Similarity	NPC222688
0.8468	Intermediate Similarity	NPC88701
0.8468	Intermediate Similarity	NPC171619
0.8468	Intermediate Similarity	NPC306265
0.8462	Intermediate Similarity	NPC472004
0.8455	Intermediate Similarity	NPC260268
0.8455	Intermediate Similarity	NPC247190
0.8455	Intermediate Similarity	NPC296945
0.8455	Intermediate Similarity	NPC302607
0.8455	Intermediate Similarity	NPC476027
0.8455	Intermediate Similarity	NPC150531
0.8455	Intermediate Similarity	NPC85829
0.8455	Intermediate Similarity	NPC116075
0.8455	Intermediate Similarity	NPC319077
0.8455	Intermediate Similarity	NPC97202
0.8455	Intermediate Similarity	NPC50692
0.8455	Intermediate Similarity	NPC214264
0.8455	Intermediate Similarity	NPC119855
0.8455	Intermediate Similarity	NPC32793
0.8455	Intermediate Similarity	NPC146857
0.8455	Intermediate Similarity	NPC171137
0.8455	Intermediate Similarity	NPC220217
0.8455	Intermediate Similarity	NPC469749
0.8455	Intermediate Similarity	NPC202167
0.8455	Intermediate Similarity	NPC49958
0.8455	Intermediate Similarity	NPC149047
0.8455	Intermediate Similarity	NPC48733
0.8455	Intermediate Similarity	NPC152695
0.8448	Intermediate Similarity	NPC257457
0.8448	Intermediate Similarity	NPC311554
0.844	Intermediate Similarity	NPC180204
0.844	Intermediate Similarity	NPC36688
0.844	Intermediate Similarity	NPC474775
0.844	Intermediate Similarity	NPC120321
0.8435	Intermediate Similarity	NPC298278
0.8421	Intermediate Similarity	NPC317210
0.8421	Intermediate Similarity	NPC73050
0.8403	Intermediate Similarity	NPC55602
0.84	Intermediate Similarity	NPC59288
0.8387	Intermediate Similarity	NPC329636
0.8378	Intermediate Similarity	NPC475060
0.8378	Intermediate Similarity	NPC220229
0.8378	Intermediate Similarity	NPC477916
0.8378	Intermediate Similarity	NPC83744
0.8378	Intermediate Similarity	NPC255387
0.8378	Intermediate Similarity	NPC131665
0.8376	Intermediate Similarity	NPC230513
0.8376	Intermediate Similarity	NPC42673
0.8376	Intermediate Similarity	NPC19028
0.8376	Intermediate Similarity	NPC9674
0.8364	Intermediate Similarity	NPC471293
0.8349	Intermediate Similarity	NPC477915
0.8349	Intermediate Similarity	NPC162973
0.8333	Intermediate Similarity	NPC280782
0.832	Intermediate Similarity	NPC194716
0.8305	Intermediate Similarity	NPC184555
0.8305	Intermediate Similarity	NPC476961
0.8304	Intermediate Similarity	NPC472825
0.8304	Intermediate Similarity	NPC189075
0.8304	Intermediate Similarity	NPC275539
0.8304	Intermediate Similarity	NPC217201
0.8304	Intermediate Similarity	NPC329417
0.8288	Intermediate Similarity	NPC472818
0.8279	Intermediate Similarity	NPC311534
0.8276	Intermediate Similarity	NPC190286
0.8273	Intermediate Similarity	NPC140723
0.8264	Intermediate Similarity	NPC15095
0.8257	Intermediate Similarity	NPC303559
0.8254	Intermediate Similarity	NPC329675
0.825	Intermediate Similarity	NPC11895
0.823	Intermediate Similarity	NPC11710
0.823	Intermediate Similarity	NPC475030
0.8224	Intermediate Similarity	NPC29952
0.8214	Intermediate Similarity	NPC110496
0.8214	Intermediate Similarity	NPC187435
0.8214	Intermediate Similarity	NPC472820
0.8214	Intermediate Similarity	NPC67321
0.8214	Intermediate Similarity	NPC59530
0.8214	Intermediate Similarity	NPC179380
0.8205	Intermediate Similarity	NPC471854
0.8205	Intermediate Similarity	NPC55296
0.8205	Intermediate Similarity	NPC152615
0.8198	Intermediate Similarity	NPC29705
0.8198	Intermediate Similarity	NPC472819
0.8197	Intermediate Similarity	NPC287423
0.819	Intermediate Similarity	NPC31354
0.819	Intermediate Similarity	NPC84949
0.819	Intermediate Similarity	NPC471633
0.819	Intermediate Similarity	NPC69576
0.8182	Intermediate Similarity	NPC172154
0.8182	Intermediate Similarity	NPC476081
0.8182	Intermediate Similarity	NPC170615
0.8182	Intermediate Similarity	NPC8369
0.8182	Intermediate Similarity	NPC81736
0.8182	Intermediate Similarity	NPC469790
0.8182	Intermediate Similarity	NPC476769
0.8182	Intermediate Similarity	NPC22388
0.8174	Intermediate Similarity	NPC126691
0.8174	Intermediate Similarity	NPC476801
0.8167	Intermediate Similarity	NPC170538
0.8165	Intermediate Similarity	NPC472826
0.8165	Intermediate Similarity	NPC476767
0.8165	Intermediate Similarity	NPC117685
0.8165	Intermediate Similarity	NPC471041
0.8151	Intermediate Similarity	NPC474585

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 NPC196931 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	199
0.1-0.2	1602
0.2-0.3	3816
0.3-0.4	2336
0.4-0.5	690
0.5-0.6	224
0.6-0.7	155
0.7-0.8	122
0.8-0.85	1
0.85-0.9	5
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8889	High Similarity	NPD7507	Approved
0.8667	High Similarity	NPD7319	Approved
0.8585	High Similarity	NPD7638	Approved
0.8505	High Similarity	NPD7640	Approved
0.8505	High Similarity	NPD7639	Approved
0.8067	Intermediate Similarity	NPD7516	Approved
0.7983	Intermediate Similarity	NPD7327	Approved
0.7983	Intermediate Similarity	NPD7328	Approved
0.7982	Intermediate Similarity	NPD7320	Approved
0.7965	Intermediate Similarity	NPD6402	Approved
0.7965	Intermediate Similarity	NPD7128	Approved
0.7965	Intermediate Similarity	NPD5739	Approved
0.7965	Intermediate Similarity	NPD6008	Approved
0.7965	Intermediate Similarity	NPD6675	Approved
0.7949	Intermediate Similarity	NPD4632	Approved
0.7913	Intermediate Similarity	NPD6372	Approved
0.7913	Intermediate Similarity	NPD6373	Approved
0.7857	Intermediate Similarity	NPD7632	Discontinued
0.7851	Intermediate Similarity	NPD8294	Approved
0.7851	Intermediate Similarity	NPD8377	Approved
0.7826	Intermediate Similarity	NPD6899	Approved
0.7826	Intermediate Similarity	NPD6881	Approved
0.7787	Intermediate Similarity	NPD8380	Approved
0.7787	Intermediate Similarity	NPD8296	Approved
0.7787	Intermediate Similarity	NPD8379	Approved
0.7787	Intermediate Similarity	NPD8033	Approved
0.7787	Intermediate Similarity	NPD8335	Approved
0.7787	Intermediate Similarity	NPD8378	Approved
0.7778	Intermediate Similarity	NPD6650	Approved
0.7778	Intermediate Similarity	NPD6649	Approved
0.7759	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.775	Intermediate Similarity	NPD7115	Discovery
0.7739	Intermediate Similarity	NPD5701	Approved
0.7739	Intermediate Similarity	NPD5697	Approved
0.7712	Intermediate Similarity	NPD6053	Discontinued
0.7712	Intermediate Similarity	NPD8297	Approved
0.7705	Intermediate Similarity	NPD6319	Approved
0.7692	Intermediate Similarity	NPD7102	Approved
0.7692	Intermediate Similarity	NPD6883	Approved
0.7692	Intermediate Similarity	NPD7290	Approved
0.7672	Intermediate Similarity	NPD6011	Approved
0.7627	Intermediate Similarity	NPD6617	Approved
0.7627	Intermediate Similarity	NPD6869	Approved
0.7627	Intermediate Similarity	NPD6847	Approved
0.7627	Intermediate Similarity	NPD6401	Clinical (unspecified phase)
0.7627	Intermediate Similarity	NPD8130	Phase 1
0.7607	Intermediate Similarity	NPD6013	Approved
0.7607	Intermediate Similarity	NPD6012	Approved
0.7607	Intermediate Similarity	NPD6014	Approved
0.7603	Intermediate Similarity	NPD6009	Approved
0.76	Intermediate Similarity	NPD7492	Approved
0.7568	Intermediate Similarity	NPD4697	Phase 3
0.7563	Intermediate Similarity	NPD6882	Approved
0.7561	Intermediate Similarity	NPD6059	Approved
0.7561	Intermediate Similarity	NPD6054	Approved
0.7559	Intermediate Similarity	NPD7736	Approved
0.7542	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.754	Intermediate Similarity	NPD6616	Approved
0.7521	Intermediate Similarity	NPD6686	Approved
0.752	Intermediate Similarity	NPD7604	Phase 2
0.75	Intermediate Similarity	NPD6083	Phase 2
0.75	Intermediate Similarity	NPD5983	Phase 2
0.75	Intermediate Similarity	NPD6084	Phase 2
0.75	Intermediate Similarity	NPD4755	Approved
0.75	Intermediate Similarity	NPD5328	Approved
0.748	Intermediate Similarity	NPD7078	Approved
0.748	Intermediate Similarity	NPD8293	Discontinued
0.7477	Intermediate Similarity	NPD6356	Clinical (unspecified phase)
0.744	Intermediate Similarity	NPD6370	Approved
0.7402	Intermediate Similarity	NPD6336	Discontinued
0.7395	Intermediate Similarity	NPD4634	Approved
0.7391	Intermediate Similarity	NPD5211	Phase 2
0.7373	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7368	Intermediate Similarity	NPD5285	Approved
0.7368	Intermediate Similarity	NPD5286	Approved
0.7368	Intermediate Similarity	NPD4700	Approved
0.7368	Intermediate Similarity	NPD4696	Approved
0.7364	Intermediate Similarity	NPD6079	Approved
0.736	Intermediate Similarity	NPD6015	Approved
0.736	Intermediate Similarity	NPD6016	Approved
0.7304	Intermediate Similarity	NPD5223	Approved
0.7302	Intermediate Similarity	NPD5988	Approved
0.7297	Intermediate Similarity	NPD6399	Phase 3
0.7297	Intermediate Similarity	NPD4202	Approved
0.7288	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.7288	Intermediate Similarity	NPD6412	Phase 2
0.7281	Intermediate Similarity	NPD4225	Approved
0.7281	Intermediate Similarity	NPD5696	Approved
0.7265	Intermediate Similarity	NPD5141	Approved
0.7258	Intermediate Similarity	NPD6335	Approved
0.7248	Intermediate Similarity	NPD6903	Approved
0.7248	Intermediate Similarity	NPD7513	Clinical (unspecified phase)
0.7241	Intermediate Similarity	NPD5226	Approved
0.7241	Intermediate Similarity	NPD5224	Approved
0.7241	Intermediate Similarity	NPD5225	Approved
0.7241	Intermediate Similarity	NPD4633	Approved
0.7236	Intermediate Similarity	NPD6274	Approved
0.7232	Intermediate Similarity	NPD7748	Approved
0.7222	Intermediate Similarity	NPD3618	Phase 1
0.7222	Intermediate Similarity	NPD5330	Approved
0.7222	Intermediate Similarity	NPD6684	Approved
0.7222	Intermediate Similarity	NPD6291	Clinical (unspecified phase)
0.7222	Intermediate Similarity	NPD7334	Approved
0.7222	Intermediate Similarity	NPD7521	Approved
0.7222	Intermediate Similarity	NPD7146	Approved
0.7222	Intermediate Similarity	NPD7503	Approved
0.7222	Intermediate Similarity	NPD6409	Approved
0.7213	Intermediate Similarity	NPD8133	Approved
0.7207	Intermediate Similarity	NPD5693	Phase 1
0.7207	Intermediate Similarity	NPD7515	Phase 2
0.7207	Intermediate Similarity	NPD8035	Phase 2
0.7207	Intermediate Similarity	NPD8034	Phase 2
0.72	Intermediate Similarity	NPD7100	Approved
0.72	Intermediate Similarity	NPD7101	Approved
0.7193	Intermediate Similarity	NPD7902	Approved
0.7179	Intermediate Similarity	NPD5174	Approved
0.7179	Intermediate Similarity	NPD4754	Approved
0.7179	Intermediate Similarity	NPD5175	Approved
0.7177	Intermediate Similarity	NPD6317	Approved
0.7168	Intermediate Similarity	NPD5695	Phase 3
0.7154	Intermediate Similarity	NPD6033	Approved
0.713	Intermediate Similarity	NPD7520	Clinical (unspecified phase)
0.712	Intermediate Similarity	NPD6313	Approved
0.712	Intermediate Similarity	NPD6314	Approved
0.7105	Intermediate Similarity	NPD5221	Approved
0.7105	Intermediate Similarity	NPD5222	Approved
0.7105	Intermediate Similarity	NPD5220	Clinical (unspecified phase)
0.7087	Intermediate Similarity	NPD6909	Approved
0.7087	Intermediate Similarity	NPD6908	Approved
0.708	Intermediate Similarity	NPD6001	Approved
0.7059	Intermediate Similarity	NPD4768	Approved
0.7059	Intermediate Similarity	NPD4767	Approved
0.7043	Intermediate Similarity	NPD5173	Approved
0.7037	Intermediate Similarity	NPD3666	Approved
0.7037	Intermediate Similarity	NPD3133	Approved
0.7037	Intermediate Similarity	NPD3665	Phase 1
0.7027	Intermediate Similarity	NPD6673	Approved
0.7027	Intermediate Similarity	NPD4753	Phase 2
0.7027	Intermediate Similarity	NPD6080	Approved
0.7027	Intermediate Similarity	NPD6904	Approved
0.7027	Intermediate Similarity	NPD6051	Approved
0.7009	Intermediate Similarity	NPD4752	Clinical (unspecified phase)
0.6977	Remote Similarity	NPD8328	Phase 3
0.6967	Remote Similarity	NPD6371	Approved
0.696	Remote Similarity	NPD6868	Approved
0.6942	Remote Similarity	NPD5128	Approved
0.6942	Remote Similarity	NPD4729	Approved
0.6942	Remote Similarity	NPD4730	Approved
0.6937	Remote Similarity	NPD6672	Approved
0.6937	Remote Similarity	NPD5737	Approved
0.693	Remote Similarity	NPD7900	Approved
0.693	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6903	Remote Similarity	NPD5284	Approved
0.6903	Remote Similarity	NPD5281	Approved
0.6881	Remote Similarity	NPD4786	Approved
0.687	Remote Similarity	NPD5210	Approved
0.687	Remote Similarity	NPD4629	Approved
0.686	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6852	Remote Similarity	NPD4223	Phase 3
0.6852	Remote Similarity	NPD4221	Approved
0.6846	Remote Similarity	NPD6067	Discontinued
0.6829	Remote Similarity	NPD5134	Clinical (unspecified phase)
0.6829	Remote Similarity	NPD5251	Approved
0.6829	Remote Similarity	NPD5169	Approved
0.6829	Remote Similarity	NPD5250	Approved
0.6829	Remote Similarity	NPD5249	Phase 3
0.6829	Remote Similarity	NPD5248	Approved
0.6829	Remote Similarity	NPD5247	Approved
0.6829	Remote Similarity	NPD5135	Approved
0.6822	Remote Similarity	NPD7525	Registered
0.6818	Remote Similarity	NPD5329	Approved
0.6814	Remote Similarity	NPD5207	Approved
0.6814	Remote Similarity	NPD5785	Approved
0.6792	Remote Similarity	NPD6114	Approved
0.6792	Remote Similarity	NPD6115	Approved
0.6792	Remote Similarity	NPD6118	Approved
0.6792	Remote Similarity	NPD6697	Approved
0.6789	Remote Similarity	NPD4788	Approved
0.6786	Remote Similarity	NPD5208	Approved
0.6774	Remote Similarity	NPD5215	Approved
0.6774	Remote Similarity	NPD5127	Approved
0.6774	Remote Similarity	NPD5217	Approved
0.6774	Remote Similarity	NPD5216	Approved
0.6757	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6757	Remote Similarity	NPD6098	Approved
0.6754	Remote Similarity	NPD6050	Approved
0.6748	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6727	Remote Similarity	NPD4197	Approved
0.6723	Remote Similarity	NPD5344	Discontinued
0.6697	Remote Similarity	NPD3667	Approved
0.6696	Remote Similarity	NPD3573	Approved
0.6692	Remote Similarity	NPD6921	Approved
0.6691	Remote Similarity	NPD6334	Approved
0.6691	Remote Similarity	NPD6333	Approved
0.6667	Remote Similarity	NPD46	Approved
0.6667	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD1694	Approved
0.6667	Remote Similarity	NPD7625	Phase 1
0.6667	Remote Similarity	NPD5692	Phase 3
0.6667	Remote Similarity	NPD6698	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