NPASS Compound

Structure

CID61442 OpenBabel06191715392D 29 31 0 0 1 0 0 0 0 0999 V2000 3.5491 1.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4152 3.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 2.5691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9511 -2.6910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8171 -1.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 -1.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 2.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 -3.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 1.8090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5491 -0.1910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6831 -1.6910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9511 1.3090 0.0000 C 0 0 2 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 1.8171 -0.1910 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6831 3.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5878 0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 0.3090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8171 -1.1910 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8171 -4.1910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4152 0.3090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 4.3090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5878 0.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3171 -2.0570 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6831 -2.6910 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 2.8090 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 9 1 0 0 0 0 2 9 1 0 0 0 0 3 10 2 0 0 0 0 4 11 1 0 0 0 0 7 13 1 0 0 0 0 7 14 1 0 0 0 0 8 12 1 0 0 0 0 8 20 1 0 0 0 0 9 18 1 0 0 0 0 10 19 1 0 0 0 0 11 22 2 0 0 0 0 11 27 1 0 0 0 0 12 15 1 0 0 0 0 12 28 1 6 0 0 0 13 20 1 6 0 0 0 13 23 1 0 0 0 0 14 21 1 6 0 0 0 14 27 1 0 0 0 0 15 10 1 6 0 0 0 15 16 1 0 0 0 0 16 17 1 0 0 0 0 16 29 1 1 0 0 0 17 20 1 6 0 0 0 17 21 1 0 0 0 0 18 24 2 0 0 0 0 18 28 1 0 0 0 0 19 25 2 0 0 0 0 19 29 1 0 0 0 0 20 5 1 6 0 0 0 21 6 1 6 0 0 0 21 26 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	410.19
Volume:	405.879
LogP:	1.516
LogD:	0.969
LogS:	-2.842
# Rotatable Bonds:	5
TPSA:	119.36
# H-Bond Aceptor:	8
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.404
Synthetic Accessibility Score:	4.781
Fsp3:	0.762
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.976
MDCK Permeability:	9.762918489286676e-05
Pgp-inhibitor:	0.974
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.01
20% Bioavailability (F20%):	0.087
30% Bioavailability (F30%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.349
Plasma Protein Binding (PPB):	35.769351959228516%
Volume Distribution (VD):	1.026
Pgp-substrate:	56.06693649291992%

ADMET: Metabolism

CYP1A2-inhibitor:	0.027
CYP1A2-substrate:	0.051
CYP2C19-inhibitor:	0.013
CYP2C19-substrate:	0.365
CYP2C9-inhibitor:	0.013
CYP2C9-substrate:	0.056
CYP2D6-inhibitor:	0.028
CYP2D6-substrate:	0.089
CYP3A4-inhibitor:	0.159
CYP3A4-substrate:	0.264

ADMET: Excretion

Clearance (CL):	4.059
Half-life (T1/2):	0.595

ADMET: Toxicity

hERG Blockers:	0.167
Human Hepatotoxicity (H-HT):	0.857
Drug-inuced Liver Injury (DILI):	0.773
AMES Toxicity:	0.038
Rat Oral Acute Toxicity:	0.895
Maximum Recommended Daily Dose:	0.329
Skin Sensitization:	0.507
Carcinogencity:	0.088
Eye Corrosion:	0.055
Eye Irritation:	0.043
Respiratory Toxicity:	0.968

Download Data

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

Natural Product: NPC61442

Natural Product ID:	NPC61442
*Common Name:**	Tithofolinolide
IUPAC Name:	[(3aR,4R,5aR,6R,8S,9S,9aS,9bS)-8-acetyloxy-6,9-dihydroxy-5a,9-dimethyl-3-methylidene-2-oxo-3a,4,5,6,7,8,9a,9b-octahydrobenzo[g][1]benzofuran-4-yl] 2-methylpropanoate
Synonyms:	tithofolinolide
Standard InCHIKey:	UABMYELNJDXARW-SYUVKRIKSA-N
Standard InCHI:	InChI=1S/C21H30O8/c1-9(2)18(24)28-12-8-20(5)13(23)7-14(27-11(4)22)21(6,26)17(20)16-15(12)10(3)19(25)29-16/h9,12-17,23,26H,3,7-8H2,1-2,4-6H3/t12-,13-,14+,15-,16+,17-,20+,21-/m1/s1
SMILES:	CC(=O)O[C@H]1C[C@@H](O)[C@]2([C@H]([C@]1(C)O)[C@H]1OC(=O)C(=C)[C@@H]1[C@@H](C2)OC(=O)C(C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL464698
PubChem CID:	10938482
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001543] Sesquiterpene lactones [CHEMONTID:0001772] Eudesmanolides, secoeudesmanolides, 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
NPO19764	Tithonia diversifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11975495]
NPO19764	Tithonia diversifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO19764	Tithonia diversifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23501116]
NPO19764	Tithonia diversifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19764	Tithonia diversifolia	Species	Asteraceae	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	2
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell Line	HL-60	Homo sapiens	IC50	=	37.4	ug.mL-1	PMID[538245]
NPT1851	Cell Line	Col2	Homo sapiens	IC50	>	20.0	ug.mL-1	PMID[538245]
NPT2	Others	Unspecified		IC50	=	40.2	ug.mL-1	PMID[538245]

☑ 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 NPC61442 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	227
0.1-0.2	1437
0.2-0.3	4617
0.3-0.4	7903
0.4-0.5	12714
0.5-0.6	6080
0.6-0.7	6633
0.7-0.8	2838
0.8-0.85	188
0.85-0.9	45
0.9-0.95	14
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9474	High Similarity	NPC473963
0.9388	High Similarity	NPC72842
0.9388	High Similarity	NPC99510
0.9368	High Similarity	NPC93245
0.9368	High Similarity	NPC473964
0.9263	High Similarity	NPC157686
0.9263	High Similarity	NPC259042
0.9158	High Similarity	NPC148000
0.9158	High Similarity	NPC469596
0.9158	High Similarity	NPC225474
0.91	High Similarity	NPC283850
0.9072	High Similarity	NPC136781
0.902	High Similarity	NPC37628
0.899	High Similarity	NPC475958
0.8958	High Similarity	NPC24861
0.8922	High Similarity	NPC78966
0.8922	High Similarity	NPC284732
0.8889	High Similarity	NPC47024
0.8878	High Similarity	NPC474395
0.8842	High Similarity	NPC475776
0.88	High Similarity	NPC308824
0.8788	High Similarity	NPC476806
0.8788	High Similarity	NPC476807
0.8776	High Similarity	NPC284518
0.8774	High Similarity	NPC477126
0.8737	High Similarity	NPC116620
0.8687	High Similarity	NPC474921
0.8673	High Similarity	NPC90014
0.8627	High Similarity	NPC156681
0.86	High Similarity	NPC216478
0.8586	High Similarity	NPC228766
0.8586	High Similarity	NPC256227
0.8586	High Similarity	NPC165528
0.8558	High Similarity	NPC187435
0.8558	High Similarity	NPC67321
0.8544	High Similarity	NPC301787
0.8542	High Similarity	NPC194642
0.8529	High Similarity	NPC164551
0.8526	High Similarity	NPC175293
0.8526	High Similarity	NPC305029
0.8515	High Similarity	NPC477655
0.8515	High Similarity	NPC477656
0.8485	Intermediate Similarity	NPC56369
0.8476	Intermediate Similarity	NPC273155
0.8469	Intermediate Similarity	NPC147272
0.8462	Intermediate Similarity	NPC222833
0.8431	Intermediate Similarity	NPC98225
0.8431	Intermediate Similarity	NPC111292
0.8431	Intermediate Similarity	NPC242666
0.8421	Intermediate Similarity	NPC9231
0.8421	Intermediate Similarity	NPC185638
0.8421	Intermediate Similarity	NPC85698
0.8411	Intermediate Similarity	NPC474846
0.8411	Intermediate Similarity	NPC469656
0.8411	Intermediate Similarity	NPC469655
0.8411	Intermediate Similarity	NPC157476
0.8396	Intermediate Similarity	NPC474243
0.8384	Intermediate Similarity	NPC473434
0.8384	Intermediate Similarity	NPC66581
0.8384	Intermediate Similarity	NPC471446
0.8384	Intermediate Similarity	NPC474841
0.8381	Intermediate Similarity	NPC166993
0.8367	Intermediate Similarity	NPC122057
0.8365	Intermediate Similarity	NPC477127
0.8364	Intermediate Similarity	NPC473590
0.835	Intermediate Similarity	NPC476081
0.8333	Intermediate Similarity	NPC181103
0.8333	Intermediate Similarity	NPC472002
0.8317	Intermediate Similarity	NPC111348
0.8302	Intermediate Similarity	NPC231278
0.8302	Intermediate Similarity	NPC218123
0.8302	Intermediate Similarity	NPC112895
0.8302	Intermediate Similarity	NPC306265
0.8302	Intermediate Similarity	NPC255082
0.8286	Intermediate Similarity	NPC138908
0.8286	Intermediate Similarity	NPC200957
0.8273	Intermediate Similarity	NPC471816
0.8265	Intermediate Similarity	NPC153853
0.8257	Intermediate Similarity	NPC49451
0.8252	Intermediate Similarity	NPC252614
0.8247	Intermediate Similarity	NPC50847
0.8241	Intermediate Similarity	NPC94650
0.8224	Intermediate Similarity	NPC42662
0.8224	Intermediate Similarity	NPC299590
0.8224	Intermediate Similarity	NPC154906
0.8211	Intermediate Similarity	NPC97505
0.8208	Intermediate Similarity	NPC143609
0.8198	Intermediate Similarity	NPC13713
0.8198	Intermediate Similarity	NPC287343
0.8198	Intermediate Similarity	NPC97908
0.8198	Intermediate Similarity	NPC474654
0.8198	Intermediate Similarity	NPC470775
0.8198	Intermediate Similarity	NPC58662
0.8198	Intermediate Similarity	NPC473968
0.8198	Intermediate Similarity	NPC176513
0.8198	Intermediate Similarity	NPC122033
0.8198	Intermediate Similarity	NPC470854
0.819	Intermediate Similarity	NPC146731
0.819	Intermediate Similarity	NPC296950
0.8174	Intermediate Similarity	NPC24651
0.8173	Intermediate Similarity	NPC472552
0.8165	Intermediate Similarity	NPC269530
0.8165	Intermediate Similarity	NPC473397
0.8165	Intermediate Similarity	NPC474516
0.8163	Intermediate Similarity	NPC77001
0.8163	Intermediate Similarity	NPC253618
0.8155	Intermediate Similarity	NPC188968
0.8148	Intermediate Similarity	NPC475134
0.8148	Intermediate Similarity	NPC100908
0.8148	Intermediate Similarity	NPC85391
0.8148	Intermediate Similarity	NPC253906
0.8148	Intermediate Similarity	NPC475563
0.8148	Intermediate Similarity	NPC5103
0.8144	Intermediate Similarity	NPC470012
0.8137	Intermediate Similarity	NPC472998
0.8137	Intermediate Similarity	NPC274793
0.8131	Intermediate Similarity	NPC208461
0.8131	Intermediate Similarity	NPC469916
0.8131	Intermediate Similarity	NPC181994
0.8131	Intermediate Similarity	NPC472439
0.8131	Intermediate Similarity	NPC94377
0.8131	Intermediate Similarity	NPC289702
0.8125	Intermediate Similarity	NPC124676
0.8125	Intermediate Similarity	NPC146280
0.8113	Intermediate Similarity	NPC111952
0.8113	Intermediate Similarity	NPC102352
0.8108	Intermediate Similarity	NPC471127
0.8108	Intermediate Similarity	NPC234858
0.8108	Intermediate Similarity	NPC96312
0.8108	Intermediate Similarity	NPC179626
0.8108	Intermediate Similarity	NPC474734
0.8108	Intermediate Similarity	NPC40632
0.8108	Intermediate Similarity	NPC328374
0.8108	Intermediate Similarity	NPC154363
0.8108	Intermediate Similarity	NPC251236
0.8095	Intermediate Similarity	NPC120321
0.8095	Intermediate Similarity	NPC209298
0.8095	Intermediate Similarity	NPC225238
0.8095	Intermediate Similarity	NPC159533
0.8095	Intermediate Similarity	NPC122811
0.8095	Intermediate Similarity	NPC277074
0.8091	Intermediate Similarity	NPC89018
0.8091	Intermediate Similarity	NPC471252
0.8091	Intermediate Similarity	NPC94509
0.8087	Intermediate Similarity	NPC67251
0.8081	Intermediate Similarity	NPC471378
0.8081	Intermediate Similarity	NPC312471
0.8077	Intermediate Similarity	NPC49532
0.8077	Intermediate Similarity	NPC472554
0.8073	Intermediate Similarity	NPC213320
0.8073	Intermediate Similarity	NPC475668
0.8073	Intermediate Similarity	NPC473921
0.8073	Intermediate Similarity	NPC475480
0.8073	Intermediate Similarity	NPC29505
0.8058	Intermediate Similarity	NPC89099
0.8058	Intermediate Similarity	NPC20479
0.8058	Intermediate Similarity	NPC28864
0.8058	Intermediate Similarity	NPC38296
0.8058	Intermediate Similarity	NPC38471
0.8058	Intermediate Similarity	NPC98837
0.8058	Intermediate Similarity	NPC162459
0.8056	Intermediate Similarity	NPC102741
0.8056	Intermediate Similarity	NPC472216
0.8056	Intermediate Similarity	NPC284828
0.8056	Intermediate Similarity	NPC131903
0.8056	Intermediate Similarity	NPC173905
0.8056	Intermediate Similarity	NPC5475
0.8053	Intermediate Similarity	NPC475775
0.8053	Intermediate Similarity	NPC476529
0.8053	Intermediate Similarity	NPC469380
0.8041	Intermediate Similarity	NPC477920
0.8037	Intermediate Similarity	NPC144854
0.8037	Intermediate Similarity	NPC3316
0.8037	Intermediate Similarity	NPC230541
0.8037	Intermediate Similarity	NPC180744
0.8036	Intermediate Similarity	NPC469684
0.8036	Intermediate Similarity	NPC98249
0.8036	Intermediate Similarity	NPC10721
0.8036	Intermediate Similarity	NPC53396
0.8036	Intermediate Similarity	NPC296822
0.8021	Intermediate Similarity	NPC130966
0.8019	Intermediate Similarity	NPC65523
0.8019	Intermediate Similarity	NPC258532
0.8018	Intermediate Similarity	NPC88867
0.8018	Intermediate Similarity	NPC299849
0.8018	Intermediate Similarity	NPC117712
0.8018	Intermediate Similarity	NPC226608
0.8018	Intermediate Similarity	NPC472400
0.8018	Intermediate Similarity	NPC73314
0.8018	Intermediate Similarity	NPC473798
0.8	Intermediate Similarity	NPC470063
0.8	Intermediate Similarity	NPC295791
0.8	Intermediate Similarity	NPC474927
0.8	Intermediate Similarity	NPC162009
0.8	Intermediate Similarity	NPC226988
0.8	Intermediate Similarity	NPC162973
0.8	Intermediate Similarity	NPC42658
0.8	Intermediate Similarity	NPC275990
0.8	Intermediate Similarity	NPC186363
0.8	Intermediate Similarity	NPC312805

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 NPC61442 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	220
0.1-0.2	1866
0.2-0.3	3782
0.3-0.4	2095
0.4-0.5	685
0.5-0.6	272
0.6-0.7	185
0.7-0.8	45
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8224	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.8148	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.8131	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.7885	Intermediate Similarity	NPD4225	Approved
0.787	Intermediate Similarity	NPD5954	Clinical (unspecified phase)
0.7636	Intermediate Similarity	NPD6686	Approved
0.7611	Intermediate Similarity	NPD8133	Approved
0.7458	Intermediate Similarity	NPD6921	Approved
0.7414	Intermediate Similarity	NPD7115	Discovery
0.7407	Intermediate Similarity	NPD5344	Discontinued
0.7383	Intermediate Similarity	NPD7638	Approved
0.7315	Intermediate Similarity	NPD7639	Approved
0.7315	Intermediate Similarity	NPD7640	Approved
0.7288	Intermediate Similarity	NPD7516	Approved
0.7257	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7227	Intermediate Similarity	NPD6319	Approved
0.7213	Intermediate Similarity	NPD7507	Approved
0.7203	Intermediate Similarity	NPD7327	Approved
0.7203	Intermediate Similarity	NPD7328	Approved
0.7177	Intermediate Similarity	NPD7319	Approved
0.7155	Intermediate Similarity	NPD4632	Approved
0.7143	Intermediate Similarity	NPD8034	Phase 2
0.7143	Intermediate Similarity	NPD8035	Phase 2
0.7069	Intermediate Similarity	NPD8297	Approved
0.7048	Intermediate Similarity	NPD6698	Approved
0.7048	Intermediate Similarity	NPD46	Approved
0.7	Intermediate Similarity	NPD6648	Approved
0.6991	Remote Similarity	NPD6008	Approved
0.6983	Remote Similarity	NPD6649	Approved
0.6983	Remote Similarity	NPD6650	Approved
0.6957	Remote Similarity	NPD6372	Approved
0.6957	Remote Similarity	NPD6373	Approved
0.693	Remote Similarity	NPD5697	Approved
0.693	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6916	Remote Similarity	NPD6399	Phase 3
0.6897	Remote Similarity	NPD6371	Approved
0.6893	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6885	Remote Similarity	NPD8296	Approved
0.6885	Remote Similarity	NPD8335	Approved
0.6885	Remote Similarity	NPD8380	Approved
0.6885	Remote Similarity	NPD8378	Approved
0.6885	Remote Similarity	NPD8033	Approved
0.6885	Remote Similarity	NPD8379	Approved
0.6875	Remote Similarity	NPD7632	Discontinued
0.687	Remote Similarity	NPD6899	Approved
0.687	Remote Similarity	NPD6881	Approved
0.6855	Remote Similarity	NPD7492	Approved
0.6842	Remote Similarity	NPD6402	Approved
0.6842	Remote Similarity	NPD7128	Approved
0.6842	Remote Similarity	NPD5739	Approved
0.6842	Remote Similarity	NPD6675	Approved
0.6833	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.6833	Remote Similarity	NPD6009	Approved
0.6818	Remote Similarity	NPD7902	Approved
0.681	Remote Similarity	NPD6014	Approved
0.681	Remote Similarity	NPD6012	Approved
0.681	Remote Similarity	NPD6013	Approved
0.6803	Remote Similarity	NPD6054	Approved
0.6803	Remote Similarity	NPD8377	Approved
0.6803	Remote Similarity	NPD8294	Approved
0.68	Remote Similarity	NPD6616	Approved
0.6783	Remote Similarity	NPD5701	Approved
0.6783	Remote Similarity	NPD6412	Phase 2
0.678	Remote Similarity	NPD6882	Approved
0.6774	Remote Similarity	NPD8328	Phase 3
0.6765	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6752	Remote Similarity	NPD7290	Approved
0.6752	Remote Similarity	NPD6883	Approved
0.6752	Remote Similarity	NPD7102	Approved
0.6748	Remote Similarity	NPD8515	Approved
0.6748	Remote Similarity	NPD8517	Approved
0.6748	Remote Similarity	NPD8513	Phase 3
0.6748	Remote Similarity	NPD8516	Approved
0.6748	Remote Similarity	NPD5983	Phase 2
0.6748	Remote Similarity	NPD6016	Approved
0.6748	Remote Similarity	NPD7503	Approved
0.6748	Remote Similarity	NPD6015	Approved
0.6746	Remote Similarity	NPD7078	Approved
0.6731	Remote Similarity	NPD1694	Approved
0.6724	Remote Similarity	NPD6011	Approved
0.6724	Remote Similarity	NPD7320	Approved
0.6697	Remote Similarity	NPD7748	Approved
0.6695	Remote Similarity	NPD6847	Approved
0.6695	Remote Similarity	NPD6617	Approved
0.6695	Remote Similarity	NPD6869	Approved
0.6695	Remote Similarity	NPD8130	Phase 1
0.6695	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.6694	Remote Similarity	NPD6370	Approved
0.6694	Remote Similarity	NPD5988	Approved
0.6693	Remote Similarity	NPD7736	Approved
0.6667	Remote Similarity	NPD3618	Phase 1
0.6667	Remote Similarity	NPD6059	Approved
0.6667	Remote Similarity	NPD7515	Phase 2
0.664	Remote Similarity	NPD7604	Phase 2
0.6637	Remote Similarity	NPD1700	Approved
0.6636	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6614	Remote Similarity	NPD8293	Discontinued
0.661	Remote Similarity	NPD4634	Approved
0.6604	Remote Similarity	NPD7524	Approved
0.6579	Remote Similarity	NPD5211	Phase 2
0.6574	Remote Similarity	NPD7838	Discovery
0.6571	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6549	Remote Similarity	NPD5286	Approved
0.6549	Remote Similarity	NPD4696	Approved
0.6549	Remote Similarity	NPD5285	Approved
0.6545	Remote Similarity	NPD7900	Approved
0.6545	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.6535	Remote Similarity	NPD6697	Approved
0.6535	Remote Similarity	NPD6115	Approved
0.6535	Remote Similarity	NPD6336	Discontinued
0.6535	Remote Similarity	NPD6114	Approved
0.6535	Remote Similarity	NPD6118	Approved
0.6518	Remote Similarity	NPD6083	Phase 2
0.6518	Remote Similarity	NPD6084	Phase 2
0.6518	Remote Similarity	NPD4755	Approved
0.65	Remote Similarity	NPD6053	Discontinued
0.6484	Remote Similarity	NPD8074	Phase 3
0.6481	Remote Similarity	NPD1695	Approved
0.6475	Remote Similarity	NPD6274	Approved
0.6466	Remote Similarity	NPD5141	Approved
0.646	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.646	Remote Similarity	NPD5696	Approved
0.6455	Remote Similarity	NPD4202	Approved
0.6442	Remote Similarity	NPD3667	Approved
0.6436	Remote Similarity	NPD6116	Phase 1
0.6435	Remote Similarity	NPD5224	Approved
0.6435	Remote Similarity	NPD5226	Approved
0.6435	Remote Similarity	NPD5225	Approved
0.6435	Remote Similarity	NPD4633	Approved
0.6417	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6404	Remote Similarity	NPD4700	Approved
0.6396	Remote Similarity	NPD5282	Discontinued
0.6381	Remote Similarity	NPD4788	Approved
0.6379	Remote Similarity	NPD5175	Approved
0.6379	Remote Similarity	NPD5174	Approved
0.6364	Remote Similarity	NPD7637	Suspended
0.6364	Remote Similarity	NPD7983	Approved
0.6364	Remote Similarity	NPD6079	Approved
0.6349	Remote Similarity	NPD6291	Clinical (unspecified phase)
0.6348	Remote Similarity	NPD5223	Approved
0.6339	Remote Similarity	NPD5695	Phase 3
0.6339	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6337	Remote Similarity	NPD6117	Approved
0.633	Remote Similarity	NPD5328	Approved
0.6321	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6321	Remote Similarity	NPD4786	Approved
0.632	Remote Similarity	NPD7100	Approved
0.632	Remote Similarity	NPD7101	Approved
0.6306	Remote Similarity	NPD5778	Approved
0.6306	Remote Similarity	NPD5779	Approved
0.6303	Remote Similarity	NPD4729	Approved
0.6303	Remote Similarity	NPD4730	Approved
0.6296	Remote Similarity	NPD3573	Approved
0.629	Remote Similarity	NPD6317	Approved
0.6288	Remote Similarity	NPD7260	Phase 2
0.6283	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.6283	Remote Similarity	NPD5221	Approved
0.6283	Remote Similarity	NPD4697	Phase 3
0.6283	Remote Similarity	NPD5222	Approved
0.6271	Remote Similarity	NPD4768	Approved
0.6271	Remote Similarity	NPD4767	Approved
0.625	Remote Similarity	NPD6067	Discontinued
0.6241	Remote Similarity	NPD6845	Suspended
0.624	Remote Similarity	NPD6335	Approved
0.624	Remote Similarity	NPD6314	Approved
0.624	Remote Similarity	NPD6313	Approved
0.6228	Remote Similarity	NPD5173	Approved
0.6226	Remote Similarity	NPD6695	Phase 3
0.6216	Remote Similarity	NPD6411	Approved
0.6216	Remote Similarity	NPD5693	Phase 1
0.6207	Remote Similarity	NPD4159	Approved
0.6204	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6204	Remote Similarity	NPD5330	Approved
0.6204	Remote Similarity	NPD6409	Approved
0.6204	Remote Similarity	NPD7146	Approved
0.6204	Remote Similarity	NPD6684	Approved
0.6204	Remote Similarity	NPD7521	Approved
0.6204	Remote Similarity	NPD7334	Approved
0.6198	Remote Similarity	NPD5248	Approved
0.6198	Remote Similarity	NPD5249	Phase 3
0.6198	Remote Similarity	NPD5247	Approved
0.6198	Remote Similarity	NPD5250	Approved
0.6198	Remote Similarity	NPD5251	Approved
0.6195	Remote Similarity	NPD5210	Approved
0.6195	Remote Similarity	NPD4629	Approved
0.6186	Remote Similarity	NPD8170	Clinical (unspecified phase)
0.6183	Remote Similarity	NPD6033	Approved
0.6182	Remote Similarity	NPD4753	Phase 2
0.6168	Remote Similarity	NPD3666	Approved
0.6168	Remote Similarity	NPD3665	Phase 1
0.6168	Remote Similarity	NPD3133	Approved
0.6167	Remote Similarity	NPD5128	Approved
0.6162	Remote Similarity	NPD7532	Clinical (unspecified phase)
0.6139	Remote Similarity	NPD6113	Clinical (unspecified phase)
0.6126	Remote Similarity	NPD5785	Approved
0.6126	Remote Similarity	NPD3168	Discontinued
0.6106	Remote Similarity	NPD6001	Approved
0.6102	Remote Similarity	NPD4754	Approved
0.6095	Remote Similarity	NPD7525	Registered
0.6094	Remote Similarity	NPD6909	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