NPASS Compound

Structure

CID323001 OpenBabel06191716172D 56 62 0 0 1 0 0 0 0 0999 V2000 -2.4777 1.0186 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7761 2.4290 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3382 -2.5105 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1177 -1.1576 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9283 -1.9271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0561 0.2067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3572 2.2194 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8457 1.4491 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4033 2.3802 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0886 -1.2157 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9750 -2.3429 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2291 -0.3171 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2401 -1.5434 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2683 -1.4820 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0828 -2.5194 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5211 0.2538 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5321 -0.9724 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6694 -0.7975 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4839 -1.8349 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2995 -1.2663 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7197 1.5213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1358 -1.6238 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1177 -0.2481 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0224 -1.8456 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2684 0.6614 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3095 2.8381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9362 1.4491 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6726 -0.0738 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7772 -0.9740 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3810 -0.3604 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6699 1.1162 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7342 -0.9388 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9054 0.2067 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3810 1.6832 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1177 1.5709 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2567 1.0682 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6624 0.6614 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2678 1.4809 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9054 1.1162 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6699 0.2067 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2678 -0.1580 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5793 0.3949 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 3.4989 -2.5893 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2684 1.5709 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1071 3.7248 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0267 3.0244 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5377 2.8654 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1144 1.8131 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6401 -1.0203 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6931 -0.2481 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1786 2.5700 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4814 0.6614 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6317 1.0941 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4083 0.7406 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3817 0.9186 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 21 2 0 0 0 0 2 21 1 0 0 0 0 4 23 1 0 0 0 0 5 24 1 0 0 0 0 6 25 1 0 0 0 0 7 26 1 0 0 0 0 8 27 1 0 0 0 0 10 12 2 0 0 0 0 10 13 1 0 0 0 0 11 14 2 0 0 0 0 11 15 1 0 0 0 0 12 16 1 0 0 0 0 13 17 2 0 0 0 0 14 18 1 0 0 0 0 15 19 2 0 0 0 0 16 28 2 0 0 0 0 17 28 1 0 0 0 0 18 29 2 0 0 0 0 19 29 1 0 0 0 0 20 22 1 0 0 0 0 20 30 1 0 0 0 0 22 3 1 1 0 0 0 22 32 1 0 0 0 0 23 33 1 0 0 0 0 23 40 1 6 0 0 0 24 43 2 0 0 0 0 24 49 1 0 0 0 0 25 44 2 0 0 0 0 25 50 1 0 0 0 0 26 45 2 0 0 0 0 26 51 1 0 0 0 0 27 46 2 0 0 0 0 27 52 1 0 0 0 0 28 36 1 0 0 0 0 29 42 1 0 0 0 0 30 40 1 1 0 0 0 30 41 1 0 0 0 0 31 34 1 0 0 0 0 31 35 1 0 0 0 0 31 40 1 6 0 0 0 32 41 1 1 0 0 0 32 49 1 0 0 0 0 33 39 1 6 0 0 0 33 50 1 0 0 0 0 34 38 1 6 0 0 0 34 51 1 0 0 0 0 35 39 1 1 0 0 0 35 53 1 0 0 0 0 36 47 2 0 0 0 0 36 54 1 0 0 0 0 37 38 1 1 0 0 0 37 41 1 0 0 0 0 37 52 1 0 0 0 0 38 9 1 6 0 0 0 38 48 1 0 0 0 0 39 21 1 6 0 0 0 39 55 1 0 0 0 0 40 56 1 6 0 0 0 41 54 1 1 0 0 0 42 53 1 0 0 0 0 42 55 1 0 0 0 0 42 56 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	776.3
Volume:	766.518
LogP:	4.265
LogD:	2.219
LogS:	-4.253
# Rotatable Bonds:	13
TPSA:	179.42
# H-Bond Aceptor:	14
# H-Bond Donor:	1
# Rings:	7
# Heavy Atoms:	14

MedChem Properties

QED Drug-Likeness Score:	0.228
Synthetic Accessibility Score:	6.758
Fsp3:	0.548
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.272
MDCK Permeability:	6.49049470666796e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.67
20% Bioavailability (F20%):	0.12
30% Bioavailability (F30%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.372
Plasma Protein Binding (PPB):	74.4435806274414%
Volume Distribution (VD):	2.15
Pgp-substrate:	21.87615394592285%

ADMET: Metabolism

CYP1A2-inhibitor:	0.02
CYP1A2-substrate:	0.056
CYP2C19-inhibitor:	0.019
CYP2C19-substrate:	0.088
CYP2C9-inhibitor:	0.097
CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.115
CYP2D6-substrate:	0.049
CYP3A4-inhibitor:	0.501
CYP3A4-substrate:	0.505

ADMET: Excretion

Clearance (CL):	2.041
Half-life (T1/2):	0.362

ADMET: Toxicity

hERG Blockers:	0.647
Human Hepatotoxicity (H-HT):	0.996
Drug-inuced Liver Injury (DILI):	0.988
AMES Toxicity:	0.099
Rat Oral Acute Toxicity:	0.24
Maximum Recommended Daily Dose:	0.132
Skin Sensitization:	0.274
Carcinogencity:	0.069
Eye Corrosion:	0.003
Eye Irritation:	0.014
Respiratory Toxicity:	0.959

Download Data

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

Natural Product: NPC323001

Natural Product ID:	NPC323001
*Common Name:**	Trigohownin D
IUPAC Name:	n.a.
Synonyms:	Trigohownin D
Standard InCHIKey:	SXKWHGICTJDZFH-ZZWHEEIISA-N
Standard InCHI:	InChI=1S/C42H48O14/c1-21(2)39-33(50-25(6)44)23(4)40-30-20-22(3)32(49-24(5)43)41(30,54-36(47)28-16-12-10-13-17-28)37(52-27(8)46)38(9,48)34(51-26(7)45)31(40)35(39)53-42(55-39,56-40)29-18-14-11-15-19-29/h10-19,22-23,30-35,37,48H,1,20H2,2-9H3/t22-,23+,30-,31-,32-,33-,34-,35+,37+,38+,39-,40-,41+,42?/m0/s1
SMILES:	CC(=O)O[C@H]1[C@@H]2[C@@]3(OC4(O[C@H]2[C@]([C@H]([C@H]3C)OC(=O)C)(O4)C(=C)C)c2ccccc2)[C@H]2[C@@]([C@@H]([C@]1(C)O)OC(=O)C)(OC(=O)c1ccccc1)[C@H]([C@H](C2)C)OC(=O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1784744
PubChem CID:	53262784
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003494] Rhamnofolane and daphnane diterpenoids

*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
NPO19424	Trigonostemon howii	Species	Euphorbiaceae	Eukaryota	n.a.	twig	n.a.	PMID[21520897]
NPO19424	Trigonostemon howii	Species	Euphorbiaceae	Eukaryota	Stems	n.a.	n.a.	PMID[23148674]
NPO19424	Trigonostemon howii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23215460]
NPO19424	Trigonostemon howii	Species	Euphorbiaceae	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

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell Line	HL-60	Homo sapiens	IC50	=	9300.0	nM	PMID[464529]

☑ 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 NPC323001 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	342
0.1-0.2	1259
0.2-0.3	2572
0.3-0.4	5467
0.4-0.5	10762
0.5-0.6	14251
0.6-0.7	6827
0.7-0.8	917
0.8-0.85	163
0.85-0.9	105
0.9-0.95	23
0.95-1	9

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC326235
0.9932	High Similarity	NPC322048
0.9932	High Similarity	NPC318447
0.9797	High Similarity	NPC309991
0.9797	High Similarity	NPC323356
0.9797	High Similarity	NPC326328
0.9797	High Similarity	NPC471138
0.9726	High Similarity	NPC471135
0.9595	High Similarity	NPC475638
0.9595	High Similarity	NPC290683
0.9595	High Similarity	NPC475548
0.9467	High Similarity	NPC319404
0.9408	High Similarity	NPC478124
0.9346	High Similarity	NPC478125
0.9231	High Similarity	NPC40138
0.9189	High Similarity	NPC76103
0.9184	High Similarity	NPC312393
0.9178	High Similarity	NPC471139
0.9128	High Similarity	NPC476173
0.9097	High Similarity	NPC66193
0.9067	High Similarity	NPC478123
0.9067	High Similarity	NPC62792
0.9067	High Similarity	NPC96308
0.9038	High Similarity	NPC471134
0.8993	High Similarity	NPC327031
0.8981	High Similarity	NPC61891
0.8973	High Similarity	NPC325078
0.894	High Similarity	NPC298072
0.8919	High Similarity	NPC472570
0.8919	High Similarity	NPC476974
0.8919	High Similarity	NPC472569
0.8919	High Similarity	NPC11685
0.8919	High Similarity	NPC125106
0.8919	High Similarity	NPC95265
0.8919	High Similarity	NPC472573
0.8919	High Similarity	NPC95810
0.8919	High Similarity	NPC163719
0.8919	High Similarity	NPC70716
0.8919	High Similarity	NPC25768
0.8919	High Similarity	NPC57628
0.8919	High Similarity	NPC188865
0.8889	High Similarity	NPC34066
0.8861	High Similarity	NPC475567
0.8861	High Similarity	NPC325732
0.8861	High Similarity	NPC324769
0.8861	High Similarity	NPC473557
0.8861	High Similarity	NPC473468
0.8859	High Similarity	NPC473088
0.8859	High Similarity	NPC472572
0.8859	High Similarity	NPC476973
0.8859	High Similarity	NPC96903
0.8859	High Similarity	NPC184817
0.8859	High Similarity	NPC158663
0.8859	High Similarity	NPC29704
0.8859	High Similarity	NPC472571
0.8859	High Similarity	NPC471104
0.8859	High Similarity	NPC200471
0.8859	High Similarity	NPC472575
0.8859	High Similarity	NPC171525
0.8859	High Similarity	NPC470159
0.8859	High Similarity	NPC70403
0.8859	High Similarity	NPC472568
0.8859	High Similarity	NPC469349
0.8859	High Similarity	NPC470157
0.8859	High Similarity	NPC174982
0.8859	High Similarity	NPC177940
0.8844	High Similarity	NPC16912
0.8839	High Similarity	NPC476784
0.8824	High Similarity	NPC472657
0.8824	High Similarity	NPC472658
0.8805	High Similarity	NPC475198
0.8805	High Similarity	NPC475531
0.8805	High Similarity	NPC475175
0.88	High Similarity	NPC48599
0.88	High Similarity	NPC474935
0.88	High Similarity	NPC240115
0.88	High Similarity	NPC209592
0.8792	High Similarity	NPC475759
0.8792	High Similarity	NPC241951
0.8792	High Similarity	NPC475122
0.8792	High Similarity	NPC470152
0.879	High Similarity	NPC43304
0.879	High Similarity	NPC477190
0.879	High Similarity	NPC477188
0.879	High Similarity	NPC275477
0.8776	High Similarity	NPC171207
0.8776	High Similarity	NPC97667
0.8766	High Similarity	NPC469422
0.875	High Similarity	NPC469448
0.875	High Similarity	NPC31829
0.8742	High Similarity	NPC477491
0.8742	High Similarity	NPC281717
0.8742	High Similarity	NPC473760
0.8725	High Similarity	NPC163087
0.8716	High Similarity	NPC97947
0.8716	High Similarity	NPC87448
0.8716	High Similarity	NPC118080
0.8716	High Similarity	NPC27377
0.8716	High Similarity	NPC41481
0.8716	High Similarity	NPC472576
0.8716	High Similarity	NPC266374
0.8716	High Similarity	NPC291599
0.8684	High Similarity	NPC301556
0.8684	High Similarity	NPC270590
0.8684	High Similarity	NPC92293
0.8684	High Similarity	NPC266265
0.8684	High Similarity	NPC476975
0.8684	High Similarity	NPC471101
0.8675	High Similarity	NPC478263
0.8675	High Similarity	NPC473602
0.8667	High Similarity	NPC34943
0.8662	High Similarity	NPC477623
0.8649	High Similarity	NPC275592
0.8649	High Similarity	NPC43241
0.8649	High Similarity	NPC473758
0.8649	High Similarity	NPC184747
0.8649	High Similarity	NPC473085
0.8649	High Similarity	NPC473613
0.8649	High Similarity	NPC147880
0.8649	High Similarity	NPC100913
0.8649	High Similarity	NPC473109
0.8649	High Similarity	NPC473060
0.8649	High Similarity	NPC200592
0.8649	High Similarity	NPC473112
0.8649	High Similarity	NPC48017
0.8649	High Similarity	NPC473081
0.8649	High Similarity	NPC211137
0.8649	High Similarity	NPC90614
0.8649	High Similarity	NPC4341
0.8649	High Similarity	NPC476094
0.8627	High Similarity	NPC470245
0.8627	High Similarity	NPC473214
0.8616	High Similarity	NPC322420
0.8609	High Similarity	NPC472556
0.8609	High Similarity	NPC478264
0.86	High Similarity	NPC191387
0.86	High Similarity	NPC131966
0.8599	High Similarity	NPC49297
0.8599	High Similarity	NPC469399
0.8591	High Similarity	NPC224491
0.859	High Similarity	NPC154675
0.8581	High Similarity	NPC475652
0.8581	High Similarity	NPC214550
0.8581	High Similarity	NPC210591
0.858	High Similarity	NPC477488
0.8571	High Similarity	NPC470153
0.8571	High Similarity	NPC469415
0.8562	High Similarity	NPC473215
0.8553	High Similarity	NPC20255
0.8553	High Similarity	NPC55744
0.8535	High Similarity	NPC181924
0.8533	High Similarity	NPC192658
0.8526	High Similarity	NPC473611
0.8526	High Similarity	NPC469398
0.8516	High Similarity	NPC477905
0.8516	High Similarity	NPC472548
0.8514	High Similarity	NPC183122
0.8514	High Similarity	NPC283375
0.8506	High Similarity	NPC475561
0.8506	High Similarity	NPC303429
0.8506	High Similarity	NPC222102
0.8506	High Similarity	NPC475417
0.8503	High Similarity	NPC195647
0.8503	High Similarity	NPC291638
0.8503	High Similarity	NPC66761
0.8503	High Similarity	NPC472577
0.8503	High Similarity	NPC17877
0.8487	Intermediate Similarity	NPC311825
0.8487	Intermediate Similarity	NPC125882
0.8487	Intermediate Similarity	NPC92867
0.8477	Intermediate Similarity	NPC270498
0.8477	Intermediate Similarity	NPC246480
0.8477	Intermediate Similarity	NPC147217
0.8477	Intermediate Similarity	NPC473673
0.8477	Intermediate Similarity	NPC191082
0.8477	Intermediate Similarity	NPC475429
0.8477	Intermediate Similarity	NPC139067
0.8477	Intermediate Similarity	NPC177340
0.8477	Intermediate Similarity	NPC91703
0.8471	Intermediate Similarity	NPC70344
0.8456	Intermediate Similarity	NPC53361
0.8456	Intermediate Similarity	NPC121268
0.8435	Intermediate Similarity	NPC474608
0.8421	Intermediate Similarity	NPC470231
0.8421	Intermediate Similarity	NPC51314
0.8421	Intermediate Similarity	NPC67777
0.8418	Intermediate Similarity	NPC469417
0.8411	Intermediate Similarity	NPC34012
0.8408	Intermediate Similarity	NPC282239
0.8408	Intermediate Similarity	NPC469730
0.8408	Intermediate Similarity	NPC469456
0.8408	Intermediate Similarity	NPC132599
0.8408	Intermediate Similarity	NPC473632
0.8408	Intermediate Similarity	NPC472549
0.84	Intermediate Similarity	NPC472547
0.84	Intermediate Similarity	NPC87934
0.84	Intermediate Similarity	NPC162613
0.8389	Intermediate Similarity	NPC327511
0.8389	Intermediate Similarity	NPC205305
0.8375	Intermediate Similarity	NPC476077

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 NPC323001 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	280
0.1-0.2	776
0.2-0.3	1561
0.3-0.4	3066
0.4-0.5	2351
0.5-0.6	909
0.6-0.7	193
0.7-0.8	13
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8303	Intermediate Similarity	NPD7799	Discontinued
0.8023	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7898	Intermediate Similarity	NPD7236	Approved
0.7764	Intermediate Similarity	NPD7239	Suspended
0.7719	Intermediate Similarity	NPD8470	Clinical (unspecified phase)
0.7682	Intermediate Similarity	NPD5952	Clinical (unspecified phase)
0.7586	Intermediate Similarity	NPD7685	Pre-registration
0.7483	Intermediate Similarity	NPD6007	Clinical (unspecified phase)
0.7458	Intermediate Similarity	NPD8407	Phase 2
0.7386	Intermediate Similarity	NPD8368	Discontinued
0.7337	Intermediate Similarity	NPD7058	Phase 2
0.7337	Intermediate Similarity	NPD7057	Phase 3
0.7308	Intermediate Similarity	NPD7966	Clinical (unspecified phase)
0.7293	Intermediate Similarity	NPD8361	Approved
0.7293	Intermediate Similarity	NPD8435	Approved
0.7293	Intermediate Similarity	NPD8360	Approved
0.7257	Intermediate Similarity	NPD7228	Approved
0.7251	Intermediate Similarity	NPD6234	Discontinued
0.7248	Intermediate Similarity	NPD5126	Approved
0.7248	Intermediate Similarity	NPD5125	Phase 3
0.7235	Intermediate Similarity	NPD4967	Phase 2
0.7235	Intermediate Similarity	NPD4965	Approved
0.7235	Intermediate Similarity	NPD4966	Approved
0.7213	Intermediate Similarity	NPD7879	Clinical (unspecified phase)
0.7196	Intermediate Similarity	NPD7497	Discontinued
0.7182	Intermediate Similarity	NPD8424	Clinical (unspecified phase)
0.7182	Intermediate Similarity	NPD8434	Phase 2
0.7168	Intermediate Similarity	NPD7199	Phase 2
0.7168	Intermediate Similarity	NPD8127	Discontinued
0.716	Intermediate Similarity	NPD37	Approved
0.7111	Intermediate Similarity	NPD8312	Approved
0.7111	Intermediate Similarity	NPD8313	Approved
0.7108	Intermediate Similarity	NPD6273	Approved
0.7095	Intermediate Similarity	NPD7240	Approved
0.7088	Intermediate Similarity	NPD8150	Discontinued
0.7086	Intermediate Similarity	NPD7457	Clinical (unspecified phase)
0.7086	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.7037	Intermediate Similarity	NPD8486	Clinical (unspecified phase)
0.7025	Intermediate Similarity	NPD7961	Discontinued
0.7022	Intermediate Similarity	NPD5844	Phase 1
0.7018	Intermediate Similarity	NPD8455	Phase 2
0.7011	Intermediate Similarity	NPD8397	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD7741	Discontinued
0.6962	Remote Similarity	NPD3764	Approved
0.6941	Remote Similarity	NPD7028	Phase 2
0.6936	Remote Similarity	NPD4868	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD7266	Discontinued
0.6919	Remote Similarity	NPD5761	Phase 2
0.6919	Remote Similarity	NPD5760	Phase 2
0.6919	Remote Similarity	NPD7819	Suspended
0.6906	Remote Similarity	NPD6559	Discontinued
0.6899	Remote Similarity	NPD7008	Discontinued
0.6886	Remote Similarity	NPD6143	Clinical (unspecified phase)
0.6882	Remote Similarity	NPD7458	Discontinued
0.6878	Remote Similarity	NPD8485	Approved
0.6867	Remote Similarity	NPD6190	Approved
0.6864	Remote Similarity	NPD6980	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD7699	Phase 2
0.6842	Remote Similarity	NPD7700	Phase 2
0.6821	Remote Similarity	NPD7516	Approved
0.6821	Remote Similarity	NPD7096	Clinical (unspecified phase)
0.6813	Remote Similarity	NPD6764	Approved
0.6813	Remote Similarity	NPD6663	Approved
0.6813	Remote Similarity	NPD6765	Approved
0.6807	Remote Similarity	NPD4628	Phase 3
0.6807	Remote Similarity	NPD8166	Discontinued
0.6804	Remote Similarity	NPD8320	Phase 1
0.6804	Remote Similarity	NPD8319	Approved
0.6803	Remote Similarity	NPD2181	Clinical (unspecified phase)
0.68	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.68	Remote Similarity	NPD7075	Discontinued
0.6784	Remote Similarity	NPD6591	Clinical (unspecified phase)
0.6774	Remote Similarity	NPD7507	Approved
0.6772	Remote Similarity	NPD6535	Approved
0.6772	Remote Similarity	NPD6534	Approved
0.6755	Remote Similarity	NPD7327	Approved
0.6755	Remote Similarity	NPD7328	Approved
0.6753	Remote Similarity	NPD7435	Discontinued
0.6752	Remote Similarity	NPD7319	Approved
0.6746	Remote Similarity	NPD8389	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD4380	Phase 2
0.674	Remote Similarity	NPD7804	Clinical (unspecified phase)
0.6734	Remote Similarity	NPD8462	Phase 1
0.6727	Remote Similarity	NPD5762	Approved
0.6727	Remote Similarity	NPD6005	Phase 3
0.6727	Remote Similarity	NPD5763	Approved
0.6727	Remote Similarity	NPD6003	Clinical (unspecified phase)
0.6727	Remote Similarity	NPD6002	Phase 3
0.6727	Remote Similarity	NPD7702	Clinical (unspecified phase)
0.6727	Remote Similarity	NPD6006	Clinical (unspecified phase)
0.6727	Remote Similarity	NPD6004	Phase 3
0.6723	Remote Similarity	NPD5494	Approved
0.6722	Remote Similarity	NPD7473	Discontinued
0.6711	Remote Similarity	NPD7094	Approved
0.6711	Remote Similarity	NPD6858	Approved
0.6703	Remote Similarity	NPD7074	Phase 3
0.6689	Remote Similarity	NPD4198	Discontinued
0.6686	Remote Similarity	NPD5808	Clinical (unspecified phase)
0.6686	Remote Similarity	NPD8443	Clinical (unspecified phase)
0.6685	Remote Similarity	NPD3818	Discontinued
0.6667	Remote Similarity	NPD6785	Approved
0.6667	Remote Similarity	NPD5736	Approved
0.6667	Remote Similarity	NPD6784	Approved
0.6667	Remote Similarity	NPD7993	Clinical (unspecified phase)
0.6648	Remote Similarity	NPD7768	Phase 2
0.6648	Remote Similarity	NPD7054	Approved
0.6648	Remote Similarity	NPD6232	Discontinued
0.6647	Remote Similarity	NPD7004	Clinical (unspecified phase)
0.6646	Remote Similarity	NPD7097	Phase 1
0.6633	Remote Similarity	NPD7874	Approved
0.6633	Remote Similarity	NPD7875	Clinical (unspecified phase)
0.6626	Remote Similarity	NPD6355	Discontinued
0.6623	Remote Similarity	NPD5951	Approved
0.6623	Remote Similarity	NPD8380	Approved
0.6623	Remote Similarity	NPD2629	Approved
0.6623	Remote Similarity	NPD8335	Approved
0.6623	Remote Similarity	NPD8379	Approved
0.6623	Remote Similarity	NPD8296	Approved
0.6623	Remote Similarity	NPD8378	Approved
0.6623	Remote Similarity	NPD8033	Approved
0.6615	Remote Similarity	NPD6823	Phase 2
0.6612	Remote Similarity	NPD7472	Approved
0.6609	Remote Similarity	NPD7411	Suspended
0.6601	Remote Similarity	NPD7610	Discontinued
0.6599	Remote Similarity	NPD7999	Approved
0.6598	Remote Similarity	NPD6782	Approved
0.6598	Remote Similarity	NPD6780	Approved
0.6598	Remote Similarity	NPD6779	Approved
0.6598	Remote Similarity	NPD6781	Approved
0.6598	Remote Similarity	NPD6778	Approved
0.6598	Remote Similarity	NPD6776	Approved
0.6598	Remote Similarity	NPD6777	Approved
0.6595	Remote Similarity	NPD7808	Phase 3
0.6595	Remote Similarity	NPD4338	Clinical (unspecified phase)
0.6593	Remote Similarity	NPD3751	Discontinued
0.6591	Remote Similarity	NPD5402	Approved
0.6582	Remote Similarity	NPD7680	Approved
0.6582	Remote Similarity	NPD7696	Phase 3
0.6582	Remote Similarity	NPD7698	Approved
0.6582	Remote Similarity	NPD7697	Approved
0.6568	Remote Similarity	NPD7274	Clinical (unspecified phase)
0.6558	Remote Similarity	NPD8294	Approved
0.6558	Remote Similarity	NPD8377	Approved
0.6556	Remote Similarity	NPD3787	Discontinued
0.6554	Remote Similarity	NPD2182	Approved
0.6548	Remote Similarity	NPD7421	Clinical (unspecified phase)
0.6548	Remote Similarity	NPD7870	Phase 2
0.6548	Remote Similarity	NPD7871	Phase 2
0.6546	Remote Similarity	NPD7237	Clinical (unspecified phase)
0.6541	Remote Similarity	NPD7251	Discontinued
0.6534	Remote Similarity	NPD2393	Clinical (unspecified phase)
0.6533	Remote Similarity	NPD7701	Phase 2
0.6531	Remote Similarity	NPD6685	Approved
0.6527	Remote Similarity	NPD2346	Discontinued
0.6517	Remote Similarity	NPD7801	Approved
0.6516	Remote Similarity	NPD7503	Approved
0.6509	Remote Similarity	NPD3750	Approved
0.6509	Remote Similarity	NPD7003	Approved
0.6509	Remote Similarity	NPD6398	Clinical (unspecified phase)
0.6502	Remote Similarity	NPD7930	Approved
0.65	Remote Similarity	NPD8151	Discontinued
0.6497	Remote Similarity	NPD3817	Phase 2
0.6494	Remote Similarity	NPD3226	Approved
0.6486	Remote Similarity	NPD6797	Phase 2
0.6484	Remote Similarity	NPD6168	Clinical (unspecified phase)
0.6484	Remote Similarity	NPD7852	Clinical (unspecified phase)
0.6484	Remote Similarity	NPD7997	Clinical (unspecified phase)
0.6484	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.6484	Remote Similarity	NPD6166	Phase 2
0.648	Remote Similarity	NPD5537	Clinical (unspecified phase)
0.6478	Remote Similarity	NPD7736	Approved
0.6477	Remote Similarity	NPD1934	Approved
0.6477	Remote Similarity	NPD6801	Discontinued
0.6474	Remote Similarity	NPD5403	Approved
0.6474	Remote Similarity	NPD7163	Clinical (unspecified phase)
0.6467	Remote Similarity	NPD2935	Discontinued
0.6467	Remote Similarity	NPD5405	Approved
0.6467	Remote Similarity	NPD5404	Approved
0.6467	Remote Similarity	NPD5408	Approved
0.6467	Remote Similarity	NPD5406	Approved
0.6458	Remote Similarity	NPD6213	Phase 3
0.6458	Remote Similarity	NPD6214	Clinical (unspecified phase)
0.6458	Remote Similarity	NPD6212	Phase 3
0.6457	Remote Similarity	NPD6599	Discontinued
0.6453	Remote Similarity	NPD2534	Approved
0.6453	Remote Similarity	NPD2533	Approved
0.6453	Remote Similarity	NPD7422	Clinical (unspecified phase)
0.6453	Remote Similarity	NPD5401	Approved
0.6453	Remote Similarity	NPD2532	Approved
0.645	Remote Similarity	NPD6674	Discontinued
0.6441	Remote Similarity	NPD1465	Phase 2
0.6439	Remote Similarity	NPD8404	Phase 2
0.6436	Remote Similarity	NPD7782	Clinical (unspecified phase)
0.6436	Remote Similarity	NPD7090	Clinical (unspecified phase)
0.6436	Remote Similarity	NPD7783	Phase 2
0.6429	Remote Similarity	NPD2343	Clinical (unspecified phase)
0.6425	Remote Similarity	NPD3749	Approved
0.6424	Remote Similarity	NPD5735	Approved
0.6424	Remote Similarity	NPD969	Suspended
0.6424	Remote Similarity	NPD230	Phase 1

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