NPASS Compound

Structure

CID4021 OpenBabel06191715322D 37 42 0 0 1 0 0 0 0 0999 V2000 8.2123 3.0124 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7385 -0.4669 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1219 -0.0158 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5752 -1.4868 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3378 -3.2987 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0934 1.9602 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2448 2.4501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0772 1.7518 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6982 0.9804 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8496 -2.4501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2448 -0.4899 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6680 1.7017 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0087 2.0544 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9421 0.4911 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5472 0.4902 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 8.7366 1.3991 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0939 0.9808 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3963 0.9805 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3958 -0.9801 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.8736 0.7937 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0006 -1.9599 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6984 -1.9604 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8491 0.4902 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5472 -0.4902 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0003 -0.9800 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 8.5329 0.4410 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2449 0.4906 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6981 -0.9804 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8491 -0.4902 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 10.3959 1.0464 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3958 -1.9812 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5644 -2.4604 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8657 -0.4800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2608 -0.2143 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8480 -2.4500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6014 0.1384 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 13 1 0 0 0 0 4 28 1 0 0 0 0 5 35 1 0 0 0 0 6 7 1 0 0 0 0 6 17 1 0 0 0 0 7 18 1 0 0 0 0 8 13 1 0 0 0 0 8 20 1 0 0 0 0 9 23 1 0 0 0 0 10 21 1 0 0 0 0 10 22 1 0 0 0 0 11 19 1 0 0 0 0 11 27 1 0 0 0 0 12 16 1 0 0 0 0 12 30 1 0 0 0 0 13 16 2 0 0 0 0 14 2 1 1 0 0 0 14 17 1 0 0 0 0 15 9 1 1 0 0 0 15 18 1 0 0 0 0 15 24 1 0 0 0 0 16 26 1 0 0 0 0 17 27 1 6 0 0 0 18 27 1 6 0 0 0 19 24 1 0 0 0 0 19 31 1 6 0 0 0 20 14 1 1 0 0 0 20 36 1 0 0 0 0 21 25 1 0 0 0 0 21 35 1 6 0 0 0 22 28 1 0 0 0 0 22 32 2 0 0 0 0 23 29 1 6 0 0 0 23 37 1 0 0 0 0 24 28 1 6 0 0 0 25 29 1 6 0 0 0 25 33 1 0 0 0 0 26 34 2 0 0 0 0 26 36 1 0 0 0 0 27 3 1 6 0 0 0 28 29 1 6 0 0 0 29 37 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	518.29
Volume:	521.214
LogP:	2.345
LogD:	2.69
LogS:	-3.989
# Rotatable Bonds:	4
TPSA:	125.82
# H-Bond Aceptor:	8
# H-Bond Donor:	3
# Rings:	6
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.293
Synthetic Accessibility Score:	6.245
Fsp3:	0.862
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:	-5.213
MDCK Permeability:	6.0220736486371607e-05
Pgp-inhibitor:	0.997
Pgp-substrate:	0.993
Human Intestinal Absorption (HIA):	0.331
20% Bioavailability (F20%):	0.014
30% Bioavailability (F30%):	0.922

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.234
Plasma Protein Binding (PPB):	39.906776428222656%
Volume Distribution (VD):	0.487
Pgp-substrate:	39.794429779052734%

ADMET: Metabolism

CYP1A2-inhibitor:	0.006
CYP1A2-substrate:	0.854
CYP2C19-inhibitor:	0.007
CYP2C19-substrate:	0.793
CYP2C9-inhibitor:	0.006
CYP2C9-substrate:	0.021
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.108
CYP3A4-inhibitor:	0.556
CYP3A4-substrate:	0.391

ADMET: Excretion

Clearance (CL):	13.31
Half-life (T1/2):	0.57

ADMET: Toxicity

hERG Blockers:	0.232
Human Hepatotoxicity (H-HT):	0.899
Drug-inuced Liver Injury (DILI):	0.367
AMES Toxicity:	0.027
Rat Oral Acute Toxicity:	0.749
Maximum Recommended Daily Dose:	0.243
Skin Sensitization:	0.314
Carcinogencity:	0.535
Eye Corrosion:	0.005
Eye Irritation:	0.012
Respiratory Toxicity:	0.977

Download Data

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

Natural Product: NPC4021

Natural Product ID:	NPC4021
*Common Name:**	Withalongolide E
IUPAC Name:	n.a.
Synonyms:	Withalongolide E
Standard InCHIKey:	JQCUJCHQCVDHTF-OAWRJLTLSA-N
Standard InCHI:	InChI=1S/C29H42O8/c1-13-8-20(36-26(34)16(13)12-30)14(2)17-6-7-18-15-9-23-29(37-23)25(33)21(35-5)10-22(32)28(29,4)24(15)19(31)11-27(17,18)3/h14-15,17-21,23-25,30-31,33H,6-12H2,1-5H3/t14-,15-,17+,18-,19-,20+,21-,23+,24+,25-,27+,28+,29-/m0/s1
SMILES:	CO[C@H]1CC(=O)[C@]2([C@]3([C@H]1O)O[C@@H]3C[C@@H]1[C@@H]2[C@@H](O)C[C@]2([C@H]1CC[C@@H]2[C@@H]([C@H]1CC(=C(C(=O)O1)CO)C)C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1934457
PubChem CID:	56926116
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
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	=	5600.0	nM	PMID[452909]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	IC50	>	10000.0	nM	PMID[452909]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[452909]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	8300.0	nM	PMID[452909]
NPT27	Others	Unspecified		IC50	=	7300.0	nM	PMID[452909]

☑ 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 NPC4021 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	299
0.1-0.2	1724
0.2-0.3	4803
0.3-0.4	7584
0.4-0.5	12027
0.5-0.6	7432
0.6-0.7	5887
0.7-0.8	2581
0.8-0.85	264
0.85-0.9	72
0.9-0.95	13
0.95-1	11

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC159456
0.991	High Similarity	NPC268530
0.991	High Similarity	NPC251226
0.991	High Similarity	NPC154491
0.9652	High Similarity	NPC120994
0.9652	High Similarity	NPC203702
0.964	High Similarity	NPC55296
0.9565	High Similarity	NPC469790
0.9469	High Similarity	NPC230513
0.9469	High Similarity	NPC42673
0.9459	High Similarity	NPC284915
0.9316	High Similarity	NPC293112
0.9153	High Similarity	NPC473635
0.9145	High Similarity	NPC469789
0.9145	High Similarity	NPC11895
0.9068	High Similarity	NPC81736
0.9068	High Similarity	NPC172154
0.906	High Similarity	NPC269642
0.906	High Similarity	NPC470265
0.906	High Similarity	NPC23786
0.906	High Similarity	NPC170538
0.8974	High Similarity	NPC67569
0.8938	High Similarity	NPC476163
0.8908	High Similarity	NPC8369
0.8803	High Similarity	NPC475041
0.8793	High Similarity	NPC58662
0.877	High Similarity	NPC231529
0.8718	High Similarity	NPC113448
0.8718	High Similarity	NPC50774
0.8718	High Similarity	NPC709
0.8684	High Similarity	NPC469655
0.8684	High Similarity	NPC469656
0.8684	High Similarity	NPC474846
0.8661	High Similarity	NPC473165
0.8632	High Similarity	NPC167606
0.8632	High Similarity	NPC286528
0.8632	High Similarity	NPC469684
0.8632	High Similarity	NPC20302
0.8632	High Similarity	NPC140055
0.8595	High Similarity	NPC8374
0.8571	High Similarity	NPC470587
0.8571	High Similarity	NPC474370
0.8559	High Similarity	NPC478206
0.8559	High Similarity	NPC108581
0.8559	High Similarity	NPC478205
0.8512	High Similarity	NPC67251
0.85	High Similarity	NPC46570
0.85	High Similarity	NPC470779
0.8496	Intermediate Similarity	NPC9457
0.8496	Intermediate Similarity	NPC471783
0.8487	Intermediate Similarity	NPC264954
0.8487	Intermediate Similarity	NPC475520
0.848	Intermediate Similarity	NPC231240
0.8475	Intermediate Similarity	NPC53396
0.8475	Intermediate Similarity	NPC312824
0.8475	Intermediate Similarity	NPC183580
0.8475	Intermediate Similarity	NPC13713
0.8475	Intermediate Similarity	NPC478204
0.8475	Intermediate Similarity	NPC98249
0.8475	Intermediate Similarity	NPC470492
0.8475	Intermediate Similarity	NPC470493
0.8468	Intermediate Similarity	NPC473593
0.8462	Intermediate Similarity	NPC67259
0.8462	Intermediate Similarity	NPC147912
0.8448	Intermediate Similarity	NPC42658
0.8448	Intermediate Similarity	NPC476964
0.8448	Intermediate Similarity	NPC269530
0.8443	Intermediate Similarity	NPC476729
0.843	Intermediate Similarity	NPC153700
0.843	Intermediate Similarity	NPC107493
0.843	Intermediate Similarity	NPC88326
0.8421	Intermediate Similarity	NPC469916
0.8421	Intermediate Similarity	NPC472439
0.8421	Intermediate Similarity	NPC273155
0.8417	Intermediate Similarity	NPC476961
0.8413	Intermediate Similarity	NPC316915
0.8403	Intermediate Similarity	NPC284707
0.8403	Intermediate Similarity	NPC240509
0.8403	Intermediate Similarity	NPC251310
0.839	Intermediate Similarity	NPC270929
0.8387	Intermediate Similarity	NPC473620
0.8376	Intermediate Similarity	NPC250109
0.8376	Intermediate Similarity	NPC317210
0.8376	Intermediate Similarity	NPC25909
0.8376	Intermediate Similarity	NPC122056
0.8376	Intermediate Similarity	NPC962
0.8361	Intermediate Similarity	NPC105926
0.8361	Intermediate Similarity	NPC91693
0.8361	Intermediate Similarity	NPC18945
0.8361	Intermediate Similarity	NPC265557
0.8347	Intermediate Similarity	NPC129434
0.8333	Intermediate Similarity	NPC61520
0.8333	Intermediate Similarity	NPC211093
0.8333	Intermediate Similarity	NPC180744
0.8333	Intermediate Similarity	NPC476960
0.8333	Intermediate Similarity	NPC77689
0.8333	Intermediate Similarity	NPC473839
0.8333	Intermediate Similarity	NPC166993
0.8333	Intermediate Similarity	NPC473636
0.8333	Intermediate Similarity	NPC112780
0.832	Intermediate Similarity	NPC476966
0.832	Intermediate Similarity	NPC470880
0.8319	Intermediate Similarity	NPC65523
0.8319	Intermediate Similarity	NPC475809
0.8319	Intermediate Similarity	NPC134430
0.8306	Intermediate Similarity	NPC117702
0.8306	Intermediate Similarity	NPC470882
0.8306	Intermediate Similarity	NPC146456
0.8306	Intermediate Similarity	NPC469757
0.8306	Intermediate Similarity	NPC287423
0.8306	Intermediate Similarity	NPC298841
0.8306	Intermediate Similarity	NPC473253
0.8306	Intermediate Similarity	NPC42399
0.8306	Intermediate Similarity	NPC471357
0.8293	Intermediate Similarity	NPC24651
0.8293	Intermediate Similarity	NPC470922
0.8293	Intermediate Similarity	NPC318135
0.8293	Intermediate Similarity	NPC3381
0.8291	Intermediate Similarity	NPC472002
0.8279	Intermediate Similarity	NPC312833
0.8279	Intermediate Similarity	NPC222688
0.8254	Intermediate Similarity	NPC173347
0.825	Intermediate Similarity	NPC329736
0.825	Intermediate Similarity	NPC473720
0.825	Intermediate Similarity	NPC186525
0.8246	Intermediate Similarity	NPC470975
0.8246	Intermediate Similarity	NPC200957
0.8246	Intermediate Similarity	NPC470979
0.8246	Intermediate Similarity	NPC103088
0.8246	Intermediate Similarity	NPC138908
0.824	Intermediate Similarity	NPC311534
0.8235	Intermediate Similarity	NPC470075
0.8235	Intermediate Similarity	NPC49492
0.8235	Intermediate Similarity	NPC16081
0.8235	Intermediate Similarity	NPC173686
0.8235	Intermediate Similarity	NPC266728
0.823	Intermediate Similarity	NPC159533
0.822	Intermediate Similarity	NPC478212
0.822	Intermediate Similarity	NPC475966
0.822	Intermediate Similarity	NPC477126
0.8211	Intermediate Similarity	NPC471392
0.8211	Intermediate Similarity	NPC204812
0.8211	Intermediate Similarity	NPC473979
0.8211	Intermediate Similarity	NPC120724
0.8211	Intermediate Similarity	NPC472399
0.8205	Intermediate Similarity	NPC94650
0.8197	Intermediate Similarity	NPC102822
0.8197	Intermediate Similarity	NPC477046
0.8197	Intermediate Similarity	NPC310511
0.819	Intermediate Similarity	NPC273433
0.819	Intermediate Similarity	NPC299590
0.8182	Intermediate Similarity	NPC473203
0.8182	Intermediate Similarity	NPC472667
0.8182	Intermediate Similarity	NPC5292
0.8182	Intermediate Similarity	NPC232258
0.8182	Intermediate Similarity	NPC473274
0.8175	Intermediate Similarity	NPC6108
0.8175	Intermediate Similarity	NPC10823
0.8175	Intermediate Similarity	NPC471358
0.8175	Intermediate Similarity	NPC471359
0.8175	Intermediate Similarity	NPC469755
0.8175	Intermediate Similarity	NPC471352
0.8175	Intermediate Similarity	NPC86159
0.8175	Intermediate Similarity	NPC197707
0.8175	Intermediate Similarity	NPC219085
0.8175	Intermediate Similarity	NPC469751
0.8175	Intermediate Similarity	NPC284406
0.8175	Intermediate Similarity	NPC251866
0.8175	Intermediate Similarity	NPC180079
0.8175	Intermediate Similarity	NPC469753
0.8175	Intermediate Similarity	NPC469754
0.8175	Intermediate Similarity	NPC17896
0.8175	Intermediate Similarity	NPC471361
0.8175	Intermediate Similarity	NPC70542
0.8175	Intermediate Similarity	NPC221414
0.8175	Intermediate Similarity	NPC89514
0.8175	Intermediate Similarity	NPC9499
0.8175	Intermediate Similarity	NPC469752
0.8175	Intermediate Similarity	NPC471360
0.8174	Intermediate Similarity	NPC67321
0.8174	Intermediate Similarity	NPC187435
0.8167	Intermediate Similarity	NPC473968
0.8167	Intermediate Similarity	NPC470854
0.8167	Intermediate Similarity	NPC470959
0.8167	Intermediate Similarity	NPC476965
0.8167	Intermediate Similarity	NPC243065
0.8167	Intermediate Similarity	NPC146432
0.8167	Intermediate Similarity	NPC470778
0.8167	Intermediate Similarity	NPC470775
0.8167	Intermediate Similarity	NPC97908
0.8167	Intermediate Similarity	NPC287343
0.8167	Intermediate Similarity	NPC176513
0.8167	Intermediate Similarity	NPC473590
0.8167	Intermediate Similarity	NPC122033
0.8167	Intermediate Similarity	NPC474654
0.816	Intermediate Similarity	NPC473265
0.8158	Intermediate Similarity	NPC301787
0.8151	Intermediate Similarity	NPC117712
0.8151	Intermediate Similarity	NPC238667
0.8151	Intermediate Similarity	NPC323821

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 NPC4021 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	279
0.1-0.2	2007
0.2-0.3	3736
0.3-0.4	1985
0.4-0.5	645
0.5-0.6	279
0.6-0.7	168
0.7-0.8	50
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8632	High Similarity	NPD7115	Discovery
0.819	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.8175	Intermediate Similarity	NPD7319	Approved
0.812	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7937	Intermediate Similarity	NPD7507	Approved
0.7863	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.7797	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.768	Intermediate Similarity	NPD6319	Approved
0.7652	Intermediate Similarity	NPD7640	Approved
0.7652	Intermediate Similarity	NPD7639	Approved
0.76	Intermediate Similarity	NPD7516	Approved
0.7565	Intermediate Similarity	NPD7638	Approved
0.7521	Intermediate Similarity	NPD7632	Discontinued
0.752	Intermediate Similarity	NPD7328	Approved
0.752	Intermediate Similarity	NPD7327	Approved
0.7479	Intermediate Similarity	NPD6008	Approved
0.744	Intermediate Similarity	NPD8295	Clinical (unspecified phase)
0.7438	Intermediate Similarity	NPD6373	Approved
0.7438	Intermediate Similarity	NPD6372	Approved
0.7414	Intermediate Similarity	NPD4225	Approved
0.7405	Intermediate Similarity	NPD7736	Approved
0.7398	Intermediate Similarity	NPD8297	Approved
0.7364	Intermediate Similarity	NPD8328	Phase 3
0.7344	Intermediate Similarity	NPD8378	Approved
0.7344	Intermediate Similarity	NPD8296	Approved
0.7344	Intermediate Similarity	NPD8033	Approved
0.7344	Intermediate Similarity	NPD8380	Approved
0.7344	Intermediate Similarity	NPD8335	Approved
0.7344	Intermediate Similarity	NPD8379	Approved
0.7339	Intermediate Similarity	NPD4632	Approved
0.7333	Intermediate Similarity	NPD7128	Approved
0.7333	Intermediate Similarity	NPD5739	Approved
0.7333	Intermediate Similarity	NPD6675	Approved
0.7333	Intermediate Similarity	NPD6402	Approved
0.7317	Intermediate Similarity	NPD6650	Approved
0.7317	Intermediate Similarity	NPD6649	Approved
0.7308	Intermediate Similarity	NPD7492	Approved
0.7295	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7266	Intermediate Similarity	NPD8377	Approved
0.7266	Intermediate Similarity	NPD6054	Approved
0.7266	Intermediate Similarity	NPD6059	Approved
0.7266	Intermediate Similarity	NPD8294	Approved
0.7252	Intermediate Similarity	NPD6616	Approved
0.7236	Intermediate Similarity	NPD6371	Approved
0.7213	Intermediate Similarity	NPD7320	Approved
0.7213	Intermediate Similarity	NPD6899	Approved
0.7213	Intermediate Similarity	NPD6881	Approved
0.7213	Intermediate Similarity	NPD6686	Approved
0.7209	Intermediate Similarity	NPD6921	Approved
0.7209	Intermediate Similarity	NPD8513	Phase 3
0.72	Intermediate Similarity	NPD8133	Approved
0.7197	Intermediate Similarity	NPD8293	Discontinued
0.7197	Intermediate Similarity	NPD7078	Approved
0.7154	Intermediate Similarity	NPD6370	Approved
0.7143	Intermediate Similarity	NPD5344	Discontinued
0.7131	Intermediate Similarity	NPD5697	Approved
0.7131	Intermediate Similarity	NPD5701	Approved
0.712	Intermediate Similarity	NPD6882	Approved
0.712	Intermediate Similarity	NPD6053	Discontinued
0.7099	Intermediate Similarity	NPD7604	Phase 2
0.7097	Intermediate Similarity	NPD4634	Approved
0.7097	Intermediate Similarity	NPD6883	Approved
0.7097	Intermediate Similarity	NPD7102	Approved
0.7097	Intermediate Similarity	NPD7290	Approved
0.7077	Intermediate Similarity	NPD6016	Approved
0.7077	Intermediate Similarity	NPD8516	Approved
0.7077	Intermediate Similarity	NPD6015	Approved
0.7077	Intermediate Similarity	NPD8515	Approved
0.7077	Intermediate Similarity	NPD8517	Approved
0.7077	Intermediate Similarity	NPD7503	Approved
0.704	Intermediate Similarity	NPD6617	Approved
0.704	Intermediate Similarity	NPD8130	Phase 1
0.704	Intermediate Similarity	NPD6847	Approved
0.704	Intermediate Similarity	NPD6869	Approved
0.7031	Intermediate Similarity	NPD6009	Approved
0.7023	Intermediate Similarity	NPD5988	Approved
0.7016	Intermediate Similarity	NPD6012	Approved
0.7016	Intermediate Similarity	NPD6013	Approved
0.7016	Intermediate Similarity	NPD6014	Approved
0.6992	Remote Similarity	NPD6412	Phase 2
0.6983	Remote Similarity	NPD6399	Phase 3
0.6957	Remote Similarity	NPD6698	Approved
0.6957	Remote Similarity	NPD46	Approved
0.6947	Remote Similarity	NPD5983	Phase 2
0.6942	Remote Similarity	NPD5211	Phase 2
0.6935	Remote Similarity	NPD6011	Approved
0.6905	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6897	Remote Similarity	NPD8035	Phase 2
0.6897	Remote Similarity	NPD8034	Phase 2
0.6891	Remote Similarity	NPD7902	Approved
0.6891	Remote Similarity	NPD4755	Approved
0.687	Remote Similarity	NPD5328	Approved
0.6866	Remote Similarity	NPD6336	Discontinued
0.6829	Remote Similarity	NPD5141	Approved
0.678	Remote Similarity	NPD7748	Approved
0.6777	Remote Similarity	NPD5285	Approved
0.6777	Remote Similarity	NPD6648	Approved
0.6777	Remote Similarity	NPD4700	Approved
0.6777	Remote Similarity	NPD5286	Approved
0.6777	Remote Similarity	NPD4696	Approved
0.6765	Remote Similarity	NPD6033	Approved
0.6752	Remote Similarity	NPD7515	Phase 2
0.6752	Remote Similarity	NPD6079	Approved
0.6752	Remote Similarity	NPD7637	Suspended
0.675	Remote Similarity	NPD6084	Phase 2
0.675	Remote Similarity	NPD6083	Phase 2
0.6721	Remote Similarity	NPD1700	Approved
0.672	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6692	Remote Similarity	NPD6274	Approved
0.6691	Remote Similarity	NPD8074	Phase 3
0.6667	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD7100	Approved
0.6667	Remote Similarity	NPD5225	Approved
0.6667	Remote Similarity	NPD5224	Approved
0.6667	Remote Similarity	NPD4633	Approved
0.6667	Remote Similarity	NPD5226	Approved
0.6667	Remote Similarity	NPD4697	Phase 3
0.6667	Remote Similarity	NPD7101	Approved
0.6641	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.664	Remote Similarity	NPD4767	Approved
0.664	Remote Similarity	NPD4768	Approved
0.6639	Remote Similarity	NPD7900	Approved
0.6639	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6619	Remote Similarity	NPD7260	Phase 2
0.6613	Remote Similarity	NPD5174	Approved
0.6613	Remote Similarity	NPD5175	Approved
0.661	Remote Similarity	NPD7983	Approved
0.6609	Remote Similarity	NPD3618	Phase 1
0.6591	Remote Similarity	NPD6335	Approved
0.6585	Remote Similarity	NPD5223	Approved
0.6585	Remote Similarity	NPD4159	Approved
0.6583	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6571	Remote Similarity	NPD6845	Suspended
0.6567	Remote Similarity	NPD6908	Approved
0.6567	Remote Similarity	NPD6909	Approved
0.656	Remote Similarity	NPD8170	Clinical (unspecified phase)
0.6557	Remote Similarity	NPD5696	Approved
0.6555	Remote Similarity	NPD5778	Approved
0.6555	Remote Similarity	NPD5779	Approved
0.6555	Remote Similarity	NPD4202	Approved
0.6552	Remote Similarity	NPD7524	Approved
0.6535	Remote Similarity	NPD4729	Approved
0.6535	Remote Similarity	NPD4730	Approved
0.6529	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6529	Remote Similarity	NPD5221	Approved
0.6529	Remote Similarity	NPD5222	Approved
0.6525	Remote Similarity	NPD5785	Approved
0.6515	Remote Similarity	NPD6317	Approved
0.6496	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6486	Remote Similarity	NPD6697	Approved
0.6486	Remote Similarity	NPD6115	Approved
0.6486	Remote Similarity	NPD6114	Approved
0.6486	Remote Similarity	NPD6118	Approved
0.648	Remote Similarity	NPD4754	Approved
0.6475	Remote Similarity	NPD5173	Approved
0.6466	Remote Similarity	NPD6313	Approved
0.6466	Remote Similarity	NPD6314	Approved
0.6466	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6446	Remote Similarity	NPD5695	Phase 3
0.6446	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6444	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6439	Remote Similarity	NPD6868	Approved
0.6435	Remote Similarity	NPD4786	Approved
0.6434	Remote Similarity	NPD5248	Approved
0.6434	Remote Similarity	NPD5251	Approved
0.6434	Remote Similarity	NPD5247	Approved
0.6434	Remote Similarity	NPD5250	Approved
0.6434	Remote Similarity	NPD5249	Phase 3
0.6406	Remote Similarity	NPD5128	Approved
0.6396	Remote Similarity	NPD6116	Phase 1
0.6387	Remote Similarity	NPD7838	Discovery
0.6356	Remote Similarity	NPD6672	Approved
0.6356	Remote Similarity	NPD5737	Approved
0.6333	Remote Similarity	NPD5693	Phase 1
0.6333	Remote Similarity	NPD6411	Approved
0.6325	Remote Similarity	NPD6409	Approved
0.6325	Remote Similarity	NPD7521	Approved
0.6325	Remote Similarity	NPD5330	Approved
0.6325	Remote Similarity	NPD7146	Approved
0.6325	Remote Similarity	NPD6684	Approved
0.6325	Remote Similarity	NPD7334	Approved
0.6306	Remote Similarity	NPD6117	Approved
0.6303	Remote Similarity	NPD4753	Phase 2
0.6293	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6271	Remote Similarity	NPD3573	Approved
0.6261	Remote Similarity	NPD3667	Approved
0.626	Remote Similarity	NPD5216	Approved
0.626	Remote Similarity	NPD5217	Approved
0.626	Remote Similarity	NPD5215	Approved
0.625	Remote Similarity	NPD7236	Approved
0.6242	Remote Similarity	NPD7799	Discontinued
0.6239	Remote Similarity	NPD1694	Approved
0.6232	Remote Similarity	NPD6067	Discontinued
0.6232	Remote Similarity	NPD7642	Approved
0.623	Remote Similarity	NPD6001	Approved
0.6228	Remote Similarity	NPD7525	Registered
0.6218	Remote Similarity	NPD6903	Approved
0.6216	Remote Similarity	NPD3703	Phase 2
0.6207	Remote Similarity	NPD6695	Phase 3
0.6198	Remote Similarity	NPD5281	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